Dr. Jennifer Lang splits most of her work life treating patients at Gates Vascular Institute and conducting research in her lab several floors up in the same building.

UB medical physics students Simon Wu and Emily Vanderbelt work with flow-through 3D-printed aneurysm models using X-rays in the Canon Stroke & Vascular Research Center, part of the University at BuffaloClinical and Translational Research Center on the Buffalo Niagara Medical Campus.

The arrangement suits her well as she continues promising research to learn if a stem cell-derived treatment can repair damaged heart tissue.

Lang, a cardiologist, and her University at Buffalo team, face a dilemma: The immune system revs into high gear when the heart suffers a serious setback, limiting the power of stem cells to heal.

The daunting task seems more surmountable these days because she works in a building filled with researchers of all stripes.

I do collaborations with groups that I otherwise wouldn't have. Its led to some really new, interesting results, said Lang, assistant professor in the UB Jacobs School of Medicine and Biomedical Sciences who practices with UBMD Internal Medicine and at the Buffalo VA Medical Center.

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This day, a surgical team worked seamlessly to monitor her vital signs and feather a medical device through a catheter into the left side of her damaged heart. The procedure slowed her heartrate so her organs could take a couple of days to re-collect themselves and give her a fighting chance to recover.

UB-fueled research unfolds on floors five through eight of the building at 875 Ellicott St., alongside Buffalo General Medical Center.

Ten years ago, the university invested $118 million into its Clinical and Translational Research Center, and about $25 million for equipment came from industry partners who wanted to join forces with physicians, engineers and others in the science fields.

The center became the first major pieceof the UB medical school to move onto the downtown Buffalo Niagara Medical Campus, followed in late 2017 by the $375 million Jacobs School teaching and research complex, around the corner at Main and High streets.

Both foster translational medicine, which combines disciplines, resources and techniques to move benchtop research to the patient bedside, eventually strengthening community health.

Langs work symbolizes the approach.

The Buffalo native can see her high school alma mater, City Honors, from her workplace. She went to Cornell University as an undergraduate and returned to Buffalo to go to medical school. Buoyed by fellow UB students, faculty and mentors, she chose to stay in the city for her internal medicine residency and cardiology fellowship.

Lang did her classroom work and research on the UB South Campus and most of her clinical work 8 miles away, on the downtown Medical Campus.

Stairs and elevators are the only things that separate her from most of her collaborators and patients today.

I moved into this building when it opened 10 years ago, she said. At the time, I was completing my cardiology fellowship. There was a physical divide, so I was thrilled with the new arrangement. Things can happen in parallel now.

Dr. Timothy Murphy, left, director of theUB Clinical and Translational Research Center in Buffalo, works with research technician Charmaine Kirkham in their lab, which focuses on potential treatments forchronic obstructive pulmonary disease (COPD).

That was the plan, said Dr. Timothy Murphy, director of the UB Clinical and Translational Research Center.

Clinical research and health care have become more and more seamlessly integrated, he said. The building contributed to that.

Murphy, another regional native, was among those who shared and helped carry out the vision of Gates Vascular Institute founder Dr. L. Nelson Nick Hopkins III, who chaired the UB Department of Neurosurgery from 1989 to 2013 and wanted to create a more innovative vascular center.

Murphy moved his lab in 2006 from the VA Medical Center near South Campus to the UB Center for Bioinformatics and Life Sciences on the Medical Campus, so he could be involved in the design of the UB research center, on floors above Gates Vascular, as well as at the Jacobs School particularly its labs.

They always talked about physicians and researchers bumping into each other, talking to each other, and having graduate students and postdocs and technicians talk to each other, Murphy said. Having done it now for all these years, I see it really does work.

He and his research team continue a 20-year study on the bacterial infection that causes COPD in hopes it will help lead to vaccines that prevent the infection and new treatments to clear the bacteria from the lower airway.

As senior associate dean forclinical and translational researchat the Jacobs School, he is also the point person for coordinating UB-related clinical trials and encouraging collisions between health care researchers on the Medical Campus and around the world.

There were 70 such trials on the Medical Campus in 2015, when the building where he works was in its infancy. Today, there are more than 200.

"Things can happen in parallel now," says Dr. Jennifer Lang, a cardiologist, researcher and University at Buffalo assistant professor who splits her research and clinical time in the same building on the Buffalo Niagara Medical Campus.

Labs focused on obstetric and gynecological advances and keys to healthy aging occupy space near his seventh-floor lab.

The Clinical and Translational Research Center was established in 2012. UB added a biobank in 2019 to store medical specimens for ongoing clinical studies.

Its collaborative framework helped UB land a $15 million Clinical and Translational Science Awardin 2015 from the National Institutes of Health (NIH) to encourage research efforts across university departments and specialties to boost innovation, speed development of medical treatments, and reduce health disparities in poor, rural and minority communities.

The five-year grant was renewed in 2020 with nearly $22 million more, encouraging Buffalo-based researchers to work with others who got awards, including researchers with Harvard, Johns Hopkins, Stanford and Yale universities.

A printer creates a 3D model, slice by slice, at the Canon Stroke & Vascular Research Center in the University at Buffalo Clinical and Translational Research Center. Lab researchers experiment with different mixtures of six polymers to make the most malleable and useful models for medical research.

Throughout the building, the goal is to improve medical devices and treatments that make an impact in the clinics and catheter suites in the Gates Vascular Institute on the floors below the research center and provide data and education that informs others, including patients.

The eighth-floor Canon Stroke & Vascular Research Center, which tops the UB research center, is a case in point.

Ciprian Chip Ionita, its director, came to UB from Romania in 1999 and worked his first dozen years on the South Campus.

We were the first ones to move in, said Ionita, assistant professor of biomedical engineering and member of the medical school's Department of Neurosurgery.

The lab was designed to help innovate and improve medical devices and neurovascular procedures.

Part of its work involves using MRIs, CT scans and other radiological images of Gates Vascular patients to create 3D-printed models of the circulatory system and heart.

3D printing created this replica of part of a patient's spinal column at the Canon Stroke & Vascular Research Center. Researchers there push the boundaries until their findings are refined to the point where they can be applied to model-making on two highly calibrated 3D printers in the Jacobs Institute downstairs from the lab that meet FDA standards. We fail up here about 90% of the time, says Ciprian Chip Ionita, lab director. They fail maybe 1%, so were testing everything that's possible.

Medical school and other lab researchers use the models produced here to better understand how anatomy and disease of former and current patients led to poor health and, in some cases, poor surgical outcomes.

Gates Vascular surgeons also can use 3D models that replicate the anatomy of patients awaiting surgery to practice feathering catheters and medical devices through bends, nooks and crannies of the blood vessels, and deploy medical devices in spines and the circulatory system as they maneuver past muscles, bones, blockages and other obstructions that might come into play.

During practice interventions, we analyze everything, Ionita said, because we can go into these models with sensors to measure blood flow, blood pressure and more.

You can create a model that says, Here's somebody who has a carotid artery that's 50% (blocked) and he's 50 years old, Ionita said. Or we can say, 'Here is a young person in their 20s, and is fully compliant, no stenosis or whatever.' And those mechanical properties are translated by the printer.

Even cadaver donors cant do that.

The goal is to lower the rate of complications and be successful in one shot during a procedure, said Ionita, who supervises up to 10 graduate biomedical engineering students, and roughly 20 undergraduate, graduate and medical school students.

Those who pay close attention to 3D models and other medical research based on data from patients treated in the building include Dr. Elad Levy, co-director of the Gates Vascular Stroke Center; Dr. Adnan Siddiqui, director of neurological and stroke services at Kaleida Health; and Dr. Vijay Iyer, medical director of cardiology and the Structural Heart Program at Kaleida. All three have ties to UB.

Even here, Ionita said, physician-scientists and other researchers see the damage that smoking, high blood pressure and living in ZIP codes where poverty is rampant can create complications that lead to worse health and surgical outcomes.

Eric Wozniak, a senior research and development technician in the Idea to Reality lab at the Jacobs Institute, uses a microscope as he works to improve catheter technology.

Doctors and staff improve treatment protocols and surgical prowess with help from those who work on the top half of the building for UB and the Jacobs Institute. The latter is named for Dr. Lawrence D. Jacobs, a Buffalo neurosurgeon whose research led to the first treatments for multiple sclerosis.

Four years after Jacobs died in 2001, his brother Jeremy, chair of the Delaware North Cos. and the UB Council, approached the university about creating a lasting memorial for the respected physician. He later signed on to the concept of creating a multidisciplinary vascular center, starting with a $10 million donation for the institute that bears the family name.

The institute includes an atrium, caf and glass-walled spaces that overlook procedure rooms on the floor below. It has 50 employees, including more than 30 biomedical and electrical engineers, who seek company-sponsored research funding, help collect data and make prototypes for clinical trials, and work with researchers to publish their work in medical journals.

In 2016, the institute was designated a 3D Printing Center of Excellence in Health Care by Israeli-based Stratasys Ltd., a leading 3D printing-maker. In early 2018, it created a proof-of-concept Idea to Reality Center, known as i2R, to further improve medical devices and surgical techniques in the vascular space.

This is our secret sauce lab, said Siddiqui, Jacobs Institute CEO. There's nothing we do downstairs that we could not do better.

This is a device designed and built in the Idea 2 Reality lab at the Jacobs Institute in Buffalo. The lab improves medical devices and technology used in vascular procedures and treatments.

Dr. Carlos Pena, who ran the FDA Neurologic Devices Division for 15 years, joined the institute staff last year to improve the chances technology conceived and designed with help from the institute gets to market.

Every company wants to talk to him, Siddiqui said. He tells them what testing needs to be done. Some of that gets done in-house. A lot of it goes to the university or, when they have a clinical trial, that gets done downstairs so the entire ecosystem is functioning, I think better than Nick Hopkins ever imagined.

Lang, the cardiologist, doesnt miss her former workday commutes. She loves the design and location of the building that sets the standard for vascular care.

Most of her days mix benchtop research in her lab and patient visits and procedures on the floors below. When there is time, she can visit her husband, Fraser Sim, neuroscience director and associate professor at the medical school.

Because we're in such close proximity to the Jacobs School now, we're also really able to engage the medical students earlier in their careers and encourage more research, Lang said. And because we're so close to the hospital, we're able to involve medical residents and fellows in our research projects much more than ever before.

University at Buffalo medical school postdoctoral research associateToubaTarvirdizadeh focuses on cardiac research in the lab of Dr. Jennifer Lang at the UB Clinical and Translational Research Center in Buffalo.

She has spent a decade trying to find better ways for a stem cell derivative that can withstand an immune response and rejuvenate heart tissue without major complications, a result that could help patients recover from a heart attack and lessen the strain of heart failure.

Four years ago, Lang and her doctoral student researcher, Kyle Mentkowski, discovered a way that lowered the immune response in mice that received the derivative.

Mentkowski, now a post-doctorate researcher at Harvard-affiliated Massachusetts General Hospital, was talking with another group of student researchers in the building when they thought it might be a good idea to bring Dr. Jessica Reynolds, an immunologist and UB medical school associate professor, into the research.

The collaboration created robust, reproducible results in mice models, Lang said, and the start of testing in human immune cells she and her colleagues hope can benefit patients within the next decade.

Collaborators now regularly get together to chat at the Jacobs Institute.

The NIH seems very interested in this as a potential clinical therapy, Lang said, but the field as a whole is still in the beginning stages of understanding where we need to go next.

Dr. Aaron Hoffman, left, University at Buffalo medical school associate professor of surgery, and Dr. Kenneth Snyder, UB associate professor of neurosurgery, chat during a break in the Jacobs Institute atrium.

UB researchers have shared some of their findings with researchers making similar inroads elsewhere, she said, and the work spawned other collaborations with Reynolds, her research team and scientists in the UB Department of Biomedical Engineering.

This type of unplanned interaction is not a unique occurrence in this building, Lang said. Our story is just one of many.

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Buffalo center fuels research that can save your life from heart disease and stroke - Buffalo News

Cardiac Stem Cells Comments Off on Buffalo center fuels research that can save your life from heart disease and stroke – Buffalo News | August 2nd, 2022

Abstract: Diabetes mellitus with hyperglycaemia is a major risk factor for malignant cardiac dysrhythmias. However, the underlying mechanisms remain unclear, especially during the embryonic developmental phase of the heart. This study investigated the effect of hyperglycaemia on the pulsatile activity of stem cell-derived cardiomyocytes. Mouse embryonic stem cells (mESCs) were differentiated into cardiac-like cells through embryoid body (EB) formation, in either baseline glucose or high glucose conditions. Action potentials (APs) were recorded using a voltage-sensitive fluorescent dye and gap junction activity was evaluated using scrape-loading lucifer yellow dye transfer assay. Molecular components were detected using immunocytochemistry and immunoblot analyses. High glucose decreased the spontaneous beating rate of EBs and shortened the duration of onset of quinidine-induced asystole. Furthermore, it altered AP amplitude, but not AP duration, and had no impact on the expression of the hyperpolarisation-activated cyclic nucleotide-gated isoform 4 (HCN4) channel nor on the EB beating rate response to ivabradine nor isoprenaline. High glucose also decreased both the intercellular spread of lucifer yellow within an EB and the expression of the cardiac gap junction protein connexin 43 as well as upregulated the expression of transforming growth factor beta 1 (TGF1) and phosphorylated Smad3. High glucose suppressed the autorhythmicity and gap junction conduction of mESC-derived cardiomyocytes, via mechanisms probably involving TGF1/Smad3 signalling. The results allude to glucotoxicity related proarrhythmic effects, with potential clinical implications in foetal diabetic cardiac disease.

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Hyperglycaemia-Induced Impairment of the Autorhythmicity and Gap Junction Activity of Mouse Embryonic Stem Cell-Derived Cardiomyocyte-Like Cells -...

Cardiac Stem Cells Comments Off on Hyperglycaemia-Induced Impairment of the Autorhythmicity and Gap Junction Activity of Mouse Embryonic Stem Cell-Derived Cardiomyocyte-Like Cells -… | July 25th, 2022

NASA and Cedars-Sinai Medical Center are launching stem cells into space. In the study, funded by NASA and being conducted by scientists at Cedars-Sinai Medical Center in Los Angeles, the stem cells have been sent into space and will orbit for just over a months time to determine whether they grow differently without G-force.

A remotely controlled container of cells, with reagents and equipment needed to remotely sustain the cells, arrived at the International Space Station over the weekend. Two queries are presented alongside the launch details: do cells age differently in low orbit and can the Earthly challenges of stem cell growth amplification be overcome in space?

The human body is comprised of a full library of cell types, cataloged by specialty and location such as the striated cardiac muscles or the branching neurons in the brain. Each of these cells began as a raw stem cell and has developed in a particular manner. The cells can multiply to become a plentiful stem cell line under the correct conditions, but laboratory settings that would generate the quantity needed for medicinal purposes pose challenges that require innovative thinking.

Despite being featured in many biologic candidates currently under research and development and in clinical trials, mass-producing stem cells for use in these therapeutics isnt feasible. To prevent conglomeration or losing the stem cells at the bottom of a reactor tank, the bioreactor must be stirred at a rate that causes probable cell death. The end result is very few stem cells suitable for therapeutic and research use. By launching stem cells into space, the Cedars-Sinai research team is hoping to overcome these production limitations.

With stem cells, the possibilities and applications are increasing each day. They can work as models for testing drug safety and efficacy, thus reducing the burden placed on animal model research, be used as regenerative cells for those that have suffered damage as a result of injury or disease and even as a basic tool to help researchers further understand the human body.

By pushing the boundaries like this, its knowledge and its science and its learning, Clive Svendsen, executive director at the Cedars-Sinai Regenerative Medicine Institute, commented. Svendsen has sent a part of himself along with the project, as the donor of the stem cells.

Various other studies are being conducted by research teams around the globe in an effort to better understand the potential of stem cells.

Just last week, researchers from the University of Malta announced the launch of a similar mission that will be conducted aboard a SpaceX craft. The Maleth II project is the second installment of the Maleth Program that is designed to evaluate how human skin tissue cell genetics react to low earth orbit. A remotely controlled biocube will orbit the Earth for 60 days while the single cells are analyzed for changes.

The student researchers at the university are being directly supported by Maltas national Research, Innovation, Development Trust and the study itself is in collaboration with the Ministry of Foreign and European Affairs, Singleron Biotechnologies

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NASA's Solution to Stem Cell Production is Out of this World - BioSpace

Cardiac Stem Cells Comments Off on NASA’s Solution to Stem Cell Production is Out of this World – BioSpace | July 25th, 2022

Human samples

Rapid harvesting of cadaveric pancreatic tissues was obtained with informed consent from next of kin, from heart-beating, brain-dead donors, with research approval from the Human Research Ethics Committee at St Vincents Hospital, Melbourne. Pancreas from individuals without and with diabetes, islet, acinar and ductal samples were obtained as part of the research consented tissues through the National Islet Transplantation Programme (at Westmead Hospital, Sydney and the St Vincents Institute, Melbourne, Australia), HREC Protocol number: 011/04. The donor characteristics of islet cell donor isolations are presented in Table 1.

Islets were purified by intraductal perfusion and digestion of the pancreases with collagenase AF-1.24 (SERVA/Nordmark, Germany) followed by purification using Ficoll density gradients.25 Purified islets, from low-density gradient fractions and acinar/ductal tissue, from high-density fractions, were cultured in Miami Media 1A (Mediatech/Corning 98021, USA) supplemented with 2.5% human serum albumin (Australian Red Cross, Melbourne, VIC, Australia), in a 37C, 5% CO2 incubator.

Total RNA from human ex vivo pancreatic cells was isolated using TRIzol (Invitrogen) and RNeasy Kit (QIAGEN) including a DNase treatment. First-strand cDNA synthesis was performed using a high-capacity cDNA Reverse Transcription Kit (Applied Biosystems) according to the manufacturers instructions. cDNA primers were designed using oligoperfect designer (Thermo Fisher Scientific), as shown in Table 2. Briefly, quantitative RT-PCR analyses were undertaken using the PrecisionFast 2 qPCR Master Mix (Primerdesign) and primers using Applied Biosystems 7500 Fast Real-Time PCR System. Each qPCR reaction contained: 6.5l qPCR Master Mix, 0.5l of forward and reverse primers, 3.5l H2O and 2l of previously synthesised cDNA, diluted 1/20. Expression levels of specific genes were tested and normalised to 18s ribosomal RNA housekeeping gene.

Modification of Histone H3 and histone-associated Ezh2 protein signals were quantified in human pancreatic ductal epithelial cells (AddexBio) by the LI-COR Odyssey assay. The cells were treated with 5 or 10M of GSK 126 (S7061, Selleckchem) for 48h. Histones and their associated proteins were examined using an acid extraction and immunoblotting as described previously.18 Protein concentrations were determined using Coomassie Reagent (Sigma) with BSA as a standard. Equal amounts (3g) of acid extract were separated by Nu-PAGE (Invitrogen), transferred to a PVDF membrane (Immobilon-FL; Millipore) and then probed with antibodies against H3K27me3 (07449, Millipore), H3K27ac (ab4729, Abcam), H3K9me3 (ab8898, Abcam), H3K9me2 (ab1220, Abcam), H3K4me3 (39159, Active Motif), Ezh2 (#4905, Cell Signaling Technology), and total histone H3 (#14269, Cell Signaling Technology). Protein blotting signals were quantified by an infra-red imaging system (Odyssey; LI-COR). Modification of Histone H3 and histone-associated Ezh2 signals were quantified using total histone H3 signal as a loading control.

Chromatin immunoprecipitation assays in human exocrine cells were performed previously described.26,27 Cells were fixed for 10min with 1% formaldehyde and quenched for 10min with glycine (0.125M) solution. Fixed cells were resuspended in sodium dodecyl (lauryl) sulfate (SDS) lysis buffer (1% SDS, 10mM EDTA, 50mM Tris-HCl pH 8.1) including a protease inhibitor cocktail (Roche Diagnostics GmBH, Mannheim, Germany) and homogenised followed by incubation on ice for 5min. Soluble samples were sonicated to 200600bp and chromatin was resuspended in ChIP Dilution Buffer (0.01% SDS, 1.1% Triton X-100, 1.2mM EDTA, 16.7mM Tris-HCl pH 8.0, and 167mM NaCl) and 20l of Dynabeads Protein A (Invitrogen, Carlsbad, CA, USA) was added and pre-cleared. H3K27me3 antibody was used for immunoprecipitation of chromatin and incubated overnight at 4C as previously described.28 Immunoprecipitated DNA were collected by magnetic isolation, washed low salt followed by high salt buffers and eluted with 0.1M NaHCO3 with 1% SDS. Protein-DNA cross-links were reversed by adding Proteinase K (Sigma, St. Louis, MO, USA) and incubation at 62C for 2h. DNA was recovered using a Qiagen MinElute column (Qiagen Inc., Valencia, CA, USA). H3K27me3 content at the promoters of the INS, INS-IGF2, NGN3 and PDX1 genes were assessed by qPCR using primers designed from the integrative ENCODE resource.29 ChIP primers are shown in Table 3.

Insulin and glucagon localisation in human islets were assessed using paraffin sections (5m thickness) of human pancreas tissue fixed in 10% neutral-buffered formalin and stained with hematoxylin and eosin (H&E) or prepared for immunohistochemistry. Insulin and glucagon were detected using Guinea Pig anti-insulin (1/100, DAKO) or mouse anti-glucagon (1/50) mAbs (polyclonal Abs, Sigma-Aldrich).

Pharmacological inhibition of EZH2, human pancreatic exocrine cells were kept untreated or stimulated with 10M GSK-126 (S7061, Selleckchem) at a cell density of 1105 per well for 24h. After 24h of treatment, fresh Miami Media was added to the cells, which were treated again with 10 GSK-126 and cultured for a further 24h. All cell incubations were performed in Miami Media 1A (Mediatech/Corning 98-021, USA) supplemented with 2.5% human serum albumin (Australian Red Cross, Melbourne, VIC, Australia), in a cell culture incubator at 37C in an atmosphere of 5% CO2 for 48h using non-treated six-well culture plates (Corning).

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Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor | Signal Transduction and Targeted Therapy - Nature.com

Cardiac Stem Cells Comments Off on Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor | Signal Transduction and Targeted Therapy – Nature.com | July 25th, 2022

Shortly after I was told I would need a heart transplant, in August 2014, a cardiac nurse visited my house. She scanned the room and noticed my exercise equipment. "You're not going to use that are you?", she asked me. "Yes", I replied, "why?"

My heart was operating at 13 percent and I was firmly told I couldn't be doing that sort of thing in my condition. The nurse said she would send round a physiotherapist called Nikki Simpson to tell me what I could and couldn't do while doctors tried to figure out what was going on with my heart.

"Nikki Simpson?" I asked. It couldn't be. The woman I had once known with the same name was training to be a hairdresser, plus she'd married and moved away.

We had first met as teenagers at a club in the north of England in 1984. I had wavy shoulder length hair and she always had some sort of red leather gear on. Usually, I'm not the sharpest knife in the drawer when it comes to flirting, but I could tell she liked me straight away.

We dated for about six months. I didn't drink much so we would go on long drives and spend time with mutual friends, but for some reason the relationship just fizzled out. Nothing bad happened, we just drifted apart.

I lived a bachelor life for a while. Eventually I got married and had my son, Robert. Nikki got married and had a baby girl. We only lived a village away from each other but I never saw her once.

When my son was eight my first marriage broke down and I cared for Robert. It was the hardest thing to do, but we had the best time of our lives. I did date when my son was younger, but nobody seemed to understand that Robert came first.

For years I'd been extremely fit, I was a plasterer by trade and had always had physical jobs. But in February, 2014, when I was doing some work putting up billboards in Leeds, I couldn't breathe and kept falling to my knees.

I visited the emergency room with my sister. I was told I had pneumonia and given a course of antibiotics. I took them for two weeks but still couldn't breathe properly, so I was told it was likely I had a respiratory condition and to visit my doctor.

After months of being referred to and from the hospital, my doctor told me he thought I had heart failure. He organized an MRI scan which showed my heart was globally dilated and operating at a fraction of its normal function. They said it was likely down to a virus, but had no idea which one.

I went back the next week and the doctor sat there, clicking away on his keyboard. He glanced across at me and said: "We need to discuss a heart transplant." There I was, this strapping Yorkshireman who doesn't drink, doesn't smoke, doesn't do anything untoward, who has a dodgy heart. I stopped listening to anything he said. I went back to my doctor who told me to stop whatever I was doing, go home and watch TV on the sofa.

I started going for various scans and a cardiac nurse began to visit me and curate my drugs, which is when she mentioned about a physio helping me.

One day in August 2014, this nurse she knocked on the door and said "The physio is on her way, but I need to ask your permission for her to treat you because you have a history." I said it was fine.

When Nikki knocked on my door, I swung it open and shouted "f*** off!" I grabbed her, sat her on the kitchen table and gave her a big kiss on the cheek.

It just sort of took off from there. We started seeing each other when she came round to treat me. I would go to the gym with her to do exercises and she would call round for a cup of tea in the evenings.

Robert was doing his first year at university studying aeronautical engineering and I was concerned because he was driving a fair distance home every day just so I wasn't at home by myself. Eventually, Nikki said she'd move in with me so Robert could go and live the dream.

It was ace having her around. Even at this point, when I thought I was dying and there was no cure for me, it was like this angel had walked through the door and made my life better.

The relationship with Nikki was great, but I was going to the hospital a lot. The tablets used to steady you and make you comfortable I just couldn't tolerate. I got to the stage where I spent so much time in the hospital the porters recognised me.

It looked like I was going to die. I had a mate who had his suit washed three times for my funeral. Whenever I saw him he would say: "Are you still here?"

In October 2017, we were watching TV when an interview with the Heart Cells Foundation came on. They'd created a stem-cell procedure which took bone marrow from a patient's pelvis then injected it straight into the heart. I wanted it.

The next day I phoned them and they said to come down for some tests. I qualified for the procedure and in November 2018 went down to St Bartholomew's Hospital in London and had the treatment. It changed my life overnight.

This horrific thing I was thinking about; someone dying and me taking their heart, wasn't going to happen anymore. That was three and a half years ago. I had thought I was going to be dead in months without a transplant.

From day one of leaving the hospital, I haven't had any problems at all. I go down for a yearly check up and the consultant wants me to have the treatment again. They've never done it twice but think they might get some good results.

Nikki has been ace throughout all of this. We're looking to get married next year. I didn't want to get married before the treatment. I didn't want to be pushed down the aisle in a wheelchair or go for a meal after and end up in an ambulance. But, now, I'm getting fit, strong and strapping, so we want to go with it.

Looking back, it seems so strange that Nikki and I parted ways. I don't know if I believe in fate, but since I was first told I'd need a heart transplant we've lost my dad, my brother, two aunties and Nikki's dad. All these people who have gone, I was supposed to go before them. My perspective on life has always been to live it today, because you don't know what's going to come tomorrow.

Barry Newman, 55, from Wakefield, was a plasterer before undergoing pioneering treatment with the Heart Cells Foundation, an independent charity which has run a small unit at St Bartholomew's Hospital since 2016. Earlier this year he carried the baton at the Commonwealth Games relay.

All views expressed in this article are the author's own.

As told to Monica Greep

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'My Teen Sweetheart And I Drifted Apart. 30 Years Later I Made a Shocking Discovery' - Newsweek

Cardiac Stem Cells Comments Off on ‘My Teen Sweetheart And I Drifted Apart. 30 Years Later I Made a Shocking Discovery’ – Newsweek | July 25th, 2022

In brief

In 2020, the European Commission began a review of the EUs rules on blood, tissues and cells (BTC) used for medical treatments and therapies. Now the Commission haspublisheda draft legislative proposal to amend the rules.

The proposal does not recommend a complete overhaul: the EU will not change its definitions of blood, tissue and cell products. Yet it does promise a significant update to the two Directives published in the early 2000s that continue to govern the use of BTC components in the EU. Most importantly, the proposed legislation would be packaged as a Regulation rather than a Directive, meaning it would have a direct effect in the Member States.

The legislation sets out quality and safety requirements for allactivitiesfrom donation to human application (unless the donations are used to manufacture medicinal products or medical devices, in which case the legislation only applies to donation, collection and testing).

In its press release, the European Commission states that every year, EU patients are treated with 25 million blood transfusions (during surgery, emergency, cancer or other care), a million cycles of medically assisted reproduction, over 35,000 transplants of stem cells (mainly for blood cancers) and hundred thousands of replacement tissues (e.g., for orthopedic, skin, cardiac or eye problems). These therapies are only available thanks to the willingness of fellow citizens to make altruistic donations.

In the EU, the collection, processing and supply of each individual unit is typically organized on a local small-scale by public services, (academic) hospitals and non-profit actors.

Afteralmost 20years in place, the legislationno longer addressesthe scientific and technicalstate of the art and needs to be updated to take into account developments that have taken place in the sector.

How is the Commission planning to change BTC legislation in the EU? Here are three key takeaways from the draft proposal.

Compensating Doctors

The tissue and cell directive currently in force explicitly permits the Member States to compensate donors of tissue and cell products for their trouble. The corresponding blood Directive, however, contains no such provision: in its absence, different countries have developed their own guidelines on blood donor compensation.

That disparity is addressed in the draft Regulation, which would allow the Member States to reimburse donors of all human-derived products for losses related to their participation in adonation through fixed-rate allowances. Improving access to plasma donation, advocates of compensation schemes hope, could help the EU to bolster its patchy stockpiles of the essential fluid.

Emergency Planning

The Covid-19 pandemic demonstrated the fragility of healthcare networks that rely heavily on external sources for their products. Supply chain disruptions are a particular threat to the availability of plasma-derived medicines in the bloc since much of the EUs plasma is imported from the USA.

With this in mind, the Commission wants the Member States to develop emergency plans to cope with supply shocks. Countries would be required to maintain lines of communication that could be used in emergencies, establish authorities responsible for distribution in critical situations, and detect risks to their continued access to substances of human origin.

Detecting Risks

As might be expected, the draft Regulation introduces measures to protect the health and privacy of donors and donees. Screening is mandated to prevent patients from receiving diseased blood or cancerous cells. Technical systems should be in place to preserve the anonymity of all parties to a BTC transfer.

The burden of safeguarding is particularly heavy where assisted reproduction is concerned. It would be up to the Member States, under the draft legislation, to detect and mitigate genetic risks posed by donated reproductive cells.

If approved, it is thought that the revisions will be endorsed by 2023, with implementation beginning in 2024.

For further information, please contact Julia Gillert of our London office.

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EU: New Blood? Proposed Revisions to the EUs Blood, Tissues and Cells Rules - GlobalComplianceNews

Cardiac Stem Cells Comments Off on EU: New Blood? Proposed Revisions to the EUs Blood, Tissues and Cells Rules – GlobalComplianceNews | July 25th, 2022

Stem Cells Market: Introduction

According to the report, the globalstem cells marketwas valued at US$11.73Bn in 2020 and is projected to expand at a CAGR of10.4%from 2021 to 2028. Stem cells are defined as specialized cells of the human body that can develop into various different kinds of cells. Stem cells can form muscle cells, brain cells and all other cells in the body. Stem cells are used to treat various illnesses in the body.

North America was the largest market for stem cells in 2020. The region dominated the global market due to substantial investments in the field, impressive economic growth, increase in incidence of target chronic diseases, and technological progress. Moreover, technological advancements, increase in access to healthcare services, and entry of new manufacturers are the other factors likely to fuel the growth of the market in North America during the forecast period.

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Asia Pacific is projected to be a highly lucrative market for stem cells during the forecast period. The market in the region is anticipated to expand at a high CAGR during the forecast period. High per capita income has increased the consumption of diagnostic and therapy products in the region. Rapid expansion of the market in the region can be attributed to numerous government initiatives undertaken to improve the health care infrastructure. The market in Asia Pacific is estimated to expand rapidly compared to other regions due to shift in base of pharmaceutical companies and clinical research industries from developed to developing regions such as China and India. Moreover, changing lifestyles and increase in urbanization in these countries have led to a gradual escalation in the incidence of lifestyle-related diseases such as cancer, diabetes, and heart diseases.

Technological Advancements to Drive Market

Several companies are developing new approaches to culturing or utilizing stem cells for various applications. Stem cell technology is a rapidly developing field that combines the efforts of cell biologists, geneticists, and clinicians, and offers hope of effective treatment for various malignant and non-malignant diseases. The stem cell technology is progressing as a result of multidisciplinary effort, and advances in this technology have stimulated a rapid growth in the understanding of embryonic and postnatal neural development.

Adult Stem Cells Segment to Dominate Global Market

In terms of product type, the global stem cells market has been classified into adult stem cells, human embryonic stem cells, and induced pluripotent stem cells. The adult stem cells segment accounted for leading share of the global market in 2020. The capability of adult stem cells to generate a large number of specialized cells lowers the risk of rejection and enables repair of damaged tissues.

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Autologous Segment to Lead Market

Based on source, the global stem cells market has been bifurcated into autologous and allogenic. The autologous segment accounted for leading share of the global market in 2020. Autologous stem cells are used from ones own body to replace damaged bone marrow and hence it is safer and is commonly being practiced.

Regenerative Medicines to be Highly Lucrative

In terms of application, the global stem cells market has been categorized into regenerative medicines (neurology, oncology, cardiology, and others) and drug discovery & development. The regenerative medicines segment accounted for major share of the global market in 2020, as regenerative medicine is a stem cell therapy and the medicines are made using stem cells in order to repair an injured tissue. Increase in the number of cardiac diseases and other health conditions drive the segment.

Therapeutics Companies Emerge as Major End-users

Based on end-user, the global stem cells market has been divided into therapeutics companies, cell & tissue banks, tools & reagents companies, and service companies. The therapeutics companies segment dominated the global stem cells market in 2020. The segment is driven by increase in usage of stem cells to treat various illnesses in the body. Therapeutic companies are increasing the utilization of stem cells for providing various therapies. However, the cell & tissue banks segment is projected to expand at a high CAGR during the forecast period. Increase in number of banks that carry out research on stem cells required for tissue & cell growth and elaborative use of stem cells to grow various cells & tissues can be attributed to the growth of the segment.

Regional Analysis

In terms of region, the global stem cells market has been segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America dominated the global stem cells market in 2020, followed by Europe. Emerging markets in Asia Pacific hold immense growth potential due to increase in income levels in emerging markets such as India and China leading to a rise in healthcare spending.

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Competition Landscape

The global stem cells market is fragmented in terms of number of players. Key players in the global market include STEMCELL Technologies, Inc., Astellas Pharma, Inc., Cellular Engineering Technologies, Inc., BioTime, Inc., Takara Bio, Inc., U.S. Stem Cell, Inc., BrainStorm Cell Therapeutics, Inc., Cytori Therapeutics, Inc., Osiris Therapeutics, Inc., and Caladrius Biosciences, Inc.

Stem Cells Market, by Application

Stem Cells Market, by End-user

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Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. The firm scrutinizes factors shaping the dynamics of demand in various markets.The insights and perspectives on the markets evaluate opportunities in various segments. The opportunities in the segments based on source, application, demographics, sales channel, and end-use are analysed, which will determine growth in the markets over the next decade.

Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision-makers, made possible by experienced teams of Analysts, Researchers, and Consultants. The proprietary data sources and various tools & techniques we use always reflect the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in all of its business reports.

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Stem Cells Market to Expand at a CAGR of 10.4% from 2021 to 2028 Travel Adventure Cinema - Travel Adventure Cinema

Cardiac Stem Cells Comments Off on Stem Cells Market to Expand at a CAGR of 10.4% from 2021 to 2028 Travel Adventure Cinema – Travel Adventure Cinema | July 25th, 2022

Wilmington, Delaware, United States, July 18, 2022 (GLOBE NEWSWIRE) -- Transparency Market Research Inc.: The market value of the global cell separation technologies market is estimated to be over US$ 20.3 Bn by 2031, according to a research report by Transparency Market Research (TMR). Hence, the market is expected expand at a CAGR of 11.9% during the forecast period, from 2022 to 2031.

According to the TMR insights on the cell separation technologies market, the prevalence of chronic disorders including obesity, diabetes, cardiac diseases, cancer, and arthritis is being increasing around the world. Some of the key reasons for this situation include the sedentary lifestyle of people, increase in the older population, and rise in cigarette smoking and alcohol consumption across many developed and developing nations. These factors are expected to help in the expansion of the cell separation technologies market during the forecast period.

Players in the global cell separation technologies market are increasing focus on the launch of next-gen products. Hence, they are seen increasing investments in R&Ds. Moreover, companies are focusing on different strategies including acquisitions and strengthening their distribution networks in order to stay ahead of the competition.

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As per the Imperial College London, chronic diseases are expected to account for approximately 41 million deaths per year, which seven out of 10 demises worldwide. Of these deaths, approximately 17 million are considered to be premature. Hence, surge in cases of chronic diseases globally is resulting into increased need for cellular therapies in order to treat such disease conditions, which, in turn, is boosting the investments toward R&Ds, creating sales opportunities in the cell separation technologies market.

Cell Separation Technologies Market: Key Findings

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Cell Separation Technologies Market: Growth Boosters

Cell Separation Technologies Market: Regional Analysis

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Cell Separation Technologies Market: Key Players

Some of the key players profiled in the report are:

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Cell Separation Technologies Market Segmentation

Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated with Latest Healthcare Research Reports by Transparency Market Research:

Cell Culture Market: Rise in outsourcing activities and expansion of biopharmaceutical manufacturers are expected to drive the cell culture market during the forecast period

Cell Culture Media, Sera, and Reagents Market: The global cell culture media, sera, and reagents market is majorly driven by growth and expansion of biotechnology & pharmaceutical companies and academic & research institutes.

Stem Cells Market: The global stem cells market is majorly driven by rising applications of stem cells in regenerative medicines. Increase in the number of chronic diseases such as cardiac diseases, diabetes, cancer, etc.

Cell Line Authentication and Characterization Tests Market: Increase in the geriatric population and surge in incidence of chronic diseases are projected to drive the global cell line authentication and characterization tests market.

CAR T-cell Therapy Market: The CAR T-cell therapy market is expected to clock a CAGR of 30.6% during the assessment period. The CAR T-cell therapy is known as a revolutionary treatment option for cancer, owing to its remarkably effective and durable clinical responses.

Cell & Tissue Preservation Market: Rise in investments in the field of regenerative medicine research is estimated to propel the market. Human blood, tissues, cells, and organs own the capability to heal damaged tissues and organs with long-term advantages.

Placental Stem Cell Therapy Market: Placental stem cell therapy market is driven by prominence in treatment of age-related disorders/diseases and increase in awareness about stem cell therapies are projected to drive the global market in the near future.

Biotherapeutics Cell Line Development Market: The market growth will be largely driven by research and development activities due to which, new solutions and technologies have gradually entered the market.

About Transparency Market Research

Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.

Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

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Cell Separation Technologies Market Expands with Rise in Prevalence of Chronic Diseases, States TMR Study - GlobeNewswire

Cardiac Stem Cells Comments Off on Cell Separation Technologies Market Expands with Rise in Prevalence of Chronic Diseases, States TMR Study – GlobeNewswire | July 25th, 2022

WILMINGTON, Del., July 21, 2022 /PRNewswire/ --An in-depth demand analysis of dental membrane and bone graft substitutes found that massive demand for resorbable bone grafting materials presents value-grab opportunity. Companies in the dental membrane and bone graft substitutes market are actively leaning on development of novel biomaterials to meet the needs of bone grafting procedures. The TMR study projects the size of the market to surpass worth of US$ 1,337 Mn by 2031.

Advancements in periodontology are catalyzing introduction of new soft tissue regeneration, as emerging trends of the dental membrane and bone graft substitutes market underscore. Moreover, dental membrane and bone graft substitutes market projections in the TMR study have found that the use of xenograft for dental bone regeneration is anticipated to rise rapidly, and will unlock lucrative avenues. The fact that xenografts are cost-effective and show good results in bone tissue regeneration will spur the popularity of products in the segment.

Increasing number of bone regeneration procedures has led to the commercialization of novel biomaterials and dental bone grafts. The application of human cell sources in bone graft substitutes is growing, thus extending the canvas for companies in the dental membrane and bone graft substitutes market. Rise in oral disorders and injuries has impelled the need for bone substitute materials that can promise long-term survival rates in the patients.

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Key Findings of Dental Membrane and Bone Graft Substitutes Market Study

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Dental Membrane and Bone Graft Substitutes Market: Key Drivers

Dental Membrane and Bone Graft Substitutes Market: Regional Growth Dynamics

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Dental Membrane and Bone Graft Substitutes Market: Key Players

High degree of fragmentation has characterized the competition landscape in the dental membrane and bone graft substitutes market, mainly due to presence of several prominent players. Some of the key players are Zimmer Biomet, OPKO Health, Inc., NovaBone Products, LLC., Nobel Biocare Services AG, Geistlich Pharma AG, Dentsply Sirona, Collagen Matrix, Inc., BioHorizons, and Institut Straumann AG.

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Dental Membrane and Bone Graft Substitutes Market Segmentation

Regions Covered

Countries

Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated withLatest Healthcare Research Reportsby Transparency Market Research:

Non-Invasive Prenatal Testing Market: Non-invasive prenatal testing market was worth around US$ 1.3 Bn in 2018. The market is likely to develop at a CAGR of 16.4% during the forecast period, from 2019 to 2027.

Cell Culture Media, Sera, and Reagents Market: The global cell culture media, sera, and reagents market is majorly driven by growth and expansion of biotechnology & pharmaceutical companies and academic & research institutes.

Stem Cells Market: The global stem cells market is majorly driven by rising applications of stem cells in regenerative medicines. Increase in the number of chronic diseases such as cardiac diseases, diabetes, cancer, etc.

Cell Line Authentication and Characterization Tests Market: Increase in the geriatric population and surge in incidence of chronic diseases are projected to drive the global cell line authentication and characterization tests market.

CAR T-cell Therapy Market: The CAR T-cell therapy market is expected to clock a CAGR of 30.6% during the assessment period. The CAR T-cell therapy is known as a revolutionary treatment option for cancer, owing to its remarkably effective and durable clinical responses.

Cell & Tissue Preservation Market: Rise in investments in the field of regenerative medicine research is estimated to propel the market. Human blood, tissues, cells, and organs own the capability to heal damaged tissues and organs with long-term advantages.

mHealth Monitoring Diagnostic Medical Devices Market: The global mHealth monitoring diagnostic medical devices market was valued at US$ 29.05 Bn in 2018 and is projected to expand at a CAGR of 20.5% from 2019 to 2027.

Pediatric Medical Devices Market: The global pediatric medical devices market was valued at US$ 21,000 Mn in 2017 and is projected to expand at a CAGR of 8.0% from 2018 to 2026.

About Transparency Market Research

Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.

Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

For More Research Insights on Leading Industries, Visit Our YouTube Channel and hit subscribe for Future Update -https://www.youtube.com/channel/UC8e-z-g23-TdDMuODiL8BKQ

Contact :Rohit BhiseyTransparency Market Research Inc.CORPORATE HEADQUARTER DOWNTOWN,1000 N. West Street,Suite 1200, Wilmington, Delaware 19801 USATel: +1-518-618-1030USA Canada Toll Free: 866-552-3453Website:https://www.transparencymarketresearch.comBlog:https://tmrblog.comEmail:sales@transparencymarketresearch.com

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Dental Membrane and Bone Graft Substitutes Market to Exceed Value of US$ 1,337 Mn by 2031 - PR Newswire UK

Cardiac Stem Cells Comments Off on Dental Membrane and Bone Graft Substitutes Market to Exceed Value of US$ 1,337 Mn by 2031 – PR Newswire UK | July 25th, 2022

Almost one out of 100 babies are born with a heart defect each year in the United States. Many of these babies will need surgery within weeks of birth, followed by more surgeries throughout their lives. Now, doctors are turning to stem cells to give big hope for little hearts.

Hypoplastic left heart syndrome is a complex congenital heart disease. It is where the left ventricle does not develop, Sunjay Kaushal, MD, Ph.D., Chief of Pediatric Cardiac Surgery at Lurie Childrens Hospital in Chicago, explained.

Hypoplastic left heart syndrome

Those newborns depend solely on their right ventricles to pump blood throughout their bodies.

Kaushal emphasizes, These babies need surgical intervention in the first weeks of life.

Between 15% and 20% of those babies will not live to see their first birthday. For the little ones who do, medications and implanted devices can help, but ultimately, those children will need a heart transplant to survive.

That right ventricle becomes tired. It doesn't pump blood efficiently, Kaushal further explains.

The latest news from around North Texas.

Pediatric cardiac surgeons at Lurie Childrens Hospital are injecting stem cells directly into the heart to revitalize the worn-out right ventricle.

We're trying to see if we can actually put stem cells in there in order to remodel, rejuvenate that right ventricle in order to pump blood more efficiently for that baby, Kaushal said.

In the long run, stem cell therapy could possibly prevent those children from needing a heart transplant at all.

Kaushal added, I think that these studies could be game-changing for our babies.

They said 38 patients will be enrolled at seven clinical sites across the United States for a phase two clinical trial this year. Researchers hope that eventually, the stem cell injections will not have to be given as an injection into the heart, but as an intravenous injection like other medicine.

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Stem Cells Used to Repair Heart Defects in Children - NBC 5 Dallas-Fort Worth

Cardiac Stem Cells Comments Off on Stem Cells Used to Repair Heart Defects in Children – NBC 5 Dallas-Fort Worth | July 16th, 2022

Your heart and lungs share a close relationship, each relying on the other to replenish your blood with oxygen, remove wastes, and move blood and nutrients around your body.

When one of these players is underperforming or damaged, the other is quickly affected.

Pneumonia is an infection in one or both lungs. The tiny air sacs (alveoli) that move gases like oxygen in and out of your blood fill with fluid or pus.

This article will explore how pneumonia can affect how well your heart works and what can happen if you already have heart disease and then develop pneumonia.

Coronary artery disease is the most common form of heart disease in the United States. It develops when cholesterol and other substances build up in your blood vessels specifically the coronary arteries that supply blood to your heart.

Many things can lead to this buildup, including diet, lifestyle choices, and genetics.

The buildup of substances in your blood vessels is dangerous on its own since it can restrict blood flow to the heart and other body parts. But its even more serious when pieces of this buildup called plaques break off from the walls of your blood vessels.

When these pieces break off, they can travel to other areas of the body like the brain or heart, cutting off the blood supply to these organs resulting in a stroke or heart attack.

On its own, pneumonia is not a heart disease. Its a lung infection caused by bacteria or viruses.

However, heart disease complications like congestive heart failure can cause a condition similar to pneumonia.

Certain types of heart failure can lead to pulmonary edema. In this case, the heart is too weak to effectively pump blood out to the body, so the blood backs up into the heart and eventually into the lungs.

As this backed-up blood builds up in the lungs, pressure in the blood vessels of your lungs increases, and it can cause fluid buildup in the alveoli.

This results in an effect similar to pneumonia, where these air sacs fill with fluid.

Pneumonia is an infection that can cause inflammation throughout the body. This inflammation can lead to other complications, including an increased risk that bits of plaque can break free from your vessel walls and lead to heart attack or stroke.

Even without existing coronary artery disease or plaque buildup, the body-wide inflammation that pneumonia triggers can cause its own problems.

Inflammation can interfere with the normal function of all kinds of systems in your body especially the heart. This makes heart failure one of the most common complications of pneumonia.

About 30% of people hospitalized with community-acquired pneumonia develop heart failure and other cardiovascular problems, but the risk isnt always immediate. Research indicates that the greatest risk of heart complications occurs in the month after a pneumonia diagnosis, and the risk can continue for up to a decade.

It can be difficult to tell when pneumonia is affecting your heart, as pneumonia and heart disease can share symptoms including:

Additional symptoms you may experience with pneumonia that are not as common with heart disease include:

Inflammation in response to a pneumonia infection has some of the greatest impact on your heart.

Although heart damage from pneumonia can happen in anyone, it affects people with preexisting heart disease the most.

Among people who develop pneumonia with preexisting heart failure, about 1.4% who are treated in the outpatient setting find their heart failure gets worse after pneumonia. That percentage increases to 24% in people with more severe pneumonia that requires hospitalization.

Aside from inflammation, some individual cardiac symptoms or complications that can develop after a bout with pneumonia include:

The relationship between pneumonia and cardiovascular disease goes both ways: Pneumonia can increase the risk of heart disease, and a history of heart disease can increase the risk of pneumonia.

One 2018 study found that people with cardiovascular diseases heart failure in particular are three times more likely than others to develop community-acquired pneumonia.

Generally, the best way to prevent problems like pneumonia and heart failure is to take care of your overall health.

This means:

People with heart disease are generally recommended to stay up-to-date on various vaccinations, too. This can prevent acute infection and its complications.

However, there may be little difference in mortality rates among people with heart failure and pneumonia who had been vaccinated against things like influenza and pneumonia.

With every heartbeat and every breath, your lungs and heart work in tandem. Infections and chronic diseases that affect one organ can affect the other.

Pneumonia can increase your risk of developing heart disease or having your existing heart disease worsen. Likewise, heart disease can increase your risk of developing several types of pneumonia.

Talk with your doctor about your overall health and how to avoid chronic heart disease and acute infections like pneumonia.

Vaccines are one part of the equation, but the best strategy involves other health and diet strategies, too.

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Pneumonia and Heart Disease: What You Should Know - Healthline

Cardiac Stem Cells Comments Off on Pneumonia and Heart Disease: What You Should Know – Healthline | July 16th, 2022

Affecting one in 5,000 male births worldwide, Duchenne Muscular Dystrophy (DMD) is a fatal genetic disorder that currently doesnt have a cure, but published research conducted at the University of Nevada, Reno School of Medicine shows promise and may lead to the eventual development of a new molecular therapeutic.

The latest, significant research finding, published in Human Molecular Genetics, February 2022, involves the small-molecule sunitinib which has been shown to mitigate DMD-related skeletal muscle disease in a number of ways.

As patients with DMD grow older, muscular dystrophy worsens, causing respiratory and cardiac muscle failure resulting in premature death. There are no effective treatments to prevent DMD-related cardiac failure, however continued research in the lab of UNR Med Professor of Pharmacology Dean Burkin is pointing to protein and molecular-based solutions, including sunitinib which is already FDA approved and used in cancer treatments.

Burkin conducted the latest research with Ph.D. student Ariany Oliveira-Santos. Based on a mouse model, they found that sunitinib improved major negative symptoms that stem from DMD, such as cardiac muscle damage, without depressing the immune system completely. Oliveira-Santos was lead author on the published results. The study was supported by a grant from the Muscular Dystrophy Association and the National Institutes of Health.

Burkins lab focuses mainly on studying two key proteins 71 integrinand laminin and understanding the role they play in muscle development and disease. The lab primarily studies two muscle-damaging diseases: DMD and Laminin-2 related congenital muscular dystrophy (LAMA2-CMD).

Were interested in the biology of the 71 integrin, that's really the central focus of [our research], Burkin said. But we also have other big interests in these muscle diseases where the integrin [protein] is normally found.

Burkin explains that through this translational research, which he also calls the lab bench to bedside approach, researchers attempt to understand the biology of a system as much as possible, and then continue through the development steps that lead to therapeutic treatments.

Patients with DMD lack dystrophin which causes progressive muscle degeneration and weakness. This means the more these muscles are used, the more damage occurs. While there are repair cells in muscles, these cells eventually tire out. Burkin and Oliveira-Santos noted that the heart, an organ being used all the time, does not have this repair system, making the damage severe in cardiac muscles as well. Currently some therapeutic approaches have been beneficial for skeletal muscles but not for the heart; therefore, its important to have a drug or treatment that can target and be beneficial to skeletal and cardiac muscle at the same time, Oliveira-Santos explained.

We looked to the electrical and mechanical function of the heart and both were improved, Oliveira-Santos said. Sunitinib helped the cardiac function [and reduced] cardiac damage, and inflammation. I don't think theres really many drugs out there that do that right now.

Oliveira-Santos remembers wanting to be a scientist as early as eight years old. She went on to earn degrees in Brazil, including a bachelors in biomedicine and a masters in the scientific fields of immunology and pharmacology as they relate to transplant rejection. While earning her masters degree, Burkin was invited to Brazil by Oliveira-Santoss supervisor to give a talk, and the two met in-person and discussed her masters project. At the time, they were studying the same molecule, but in different models, so Oliveira-Santos had read some of Burkins papers.

Oliveira-Santos had always been interested in the physiology and pathology of disease and thought it would be a great area to study for a doctoral degree. She knew Burkin was working in this field, so about five years after their in-person meeting, Oliveira-Santos reached out to Burkin. He told her about an open position in his lab for a Ph.D. student, and their project of understanding the role of an FDA-approved small molecule for the treatment of DMD cardiomyopathy. She felt this project was a good match for what she was looking for and joined the lab in January 2019.

Oliveira-Santos said the mentorship and support shes received from Burkin and the rest of the lab has been invaluable.

Dean is always available to discuss and very happy to help [the lab members] with everything we need, Oliveira-Santos said. Everyone had an important opinion about the project and that was essential for the projects success.

While working in science oftentimes can come with struggles, Oliveira-Santos expressed how much these experiences have taught her.

Being in science is a big challenge, because you have to learn how to deal with problems all the time, she said. There are more failures than success [so] it teaches you how to deal with failure. Failure is normal. You just need to try to find a way around to get a solution.

Oliveira-Santos is set to finish her Ph.D. in Cellular and Molecular Pharmacology & Physiology in the fall 2022.

When I bring a student to the lab, I say I can supply everything but enthusiasm. And that's one thing that Ariany brings in abundance, Burkin said. I'm putting my students in contact with other principal investigators that I know to try and make sure that the next level on their career is achieved. She can go anywhere right now and move forward. The world is her oyster.

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Promising solution to fatal genetic-disorder complications discovered by University professor and Ph.D. candidate - Nevada Today

Cardiac Stem Cells Comments Off on Promising solution to fatal genetic-disorder complications discovered by University professor and Ph.D. candidate – Nevada Today | July 16th, 2022

After reading this article, you should be able to:

A wound is any injury that disrupts the structure of healthy skin tissue caused by chemical, mechanical, biological or thermal trauma. Wounds can be classified as acute or chronic, depending on their period of healing[1]. Acute wounds usually heal without complication within ten days; however, chronic wounds do not undergo normal healing processes, commonly have exaggerated inflammation, persistent infections or microbial biofilm formation and persist longer than six weeks[24]. The most frequent causes of chronic wounds are pressure, diabetes and vascular diseases[5].

Chronic wounds are a global problem, with annual cases rising dramatically owing to the ageing population and increased prevalence of diabetes and obesity[6]. It is estimated that up to 7% of the UK adult population has a chronic wound, costing the NHS 8.3bn each year in staff costs, wound dressings and medication[7]. Individual costs for wound management have been reported to vary, from 358 to 4,684 per patient for a wound that follows the normal healing trajectory, increasing to 831 to 7,886 per patient for a chronic, non-healing wound[7]. The majority of the costs account for GP and nursing time, with infected wounds costing an additional 1.39bn on antibiotics[7].

Results from one study, published in 2020, found that 59% of chronic wounds healed if there was no evidence of infection, compared with 45% if infection was present or suspected[7].Health conditions, such as diabetes mellitus and vascular disease, can predispose people to wounds that are difficult to heal, which can become chronic unless the underlying causes are addressed. For example, people with diabetes are prone to have a high incidence of wounds on their feet, which are slow to heal because of the impact of diabetes on the immune system, circulation and diabetic neuropathy. Complex chronic wounds, such as venous leg ulcers and diabetic ulcers, can significantly impact quality of life, morbidity and mortality[7].

Wound healing is a complex series of physiological reactions and interactions between numerous cell types and chemical mediators[8,9]. It comprises four coordinated and overlapping phases: haemostasis, inflammation, proliferation and remodelling[10].

The Figure below shows the phases of wound healing[11].

The first stage, haemostasis, is instantly activated after injury to stop bleeding at the site and prevent the entry of pathogens. In primary haemostasis, within seconds of an injury occurring, damaged blood vessels vasoconstrict to reduce blood flow through the wound area and diminish blood loss. Platelets adhere to the sub-endothelium of the impaired vessels, initiated by the presence of von Willebrand factor. This binds to glycoprotein Ib receptors on the surface of platelets, causing a conformational change on the platelet surface, activating platelets. These activated platelets release chemicals, such as adenosine diphosphate,serotonin andthromboxane A2, from their dense granules to stimulate platelet recruitment and adhesion to form a platelet plug[12,13]. Secondary haemostasis is a sequence of events, described as a coagulation cascade, that consequently converts soluble fibrinogen into insoluble fibrin. A fibrin mesh sticks to the platelet plug producing a haemostatic plug to seal the inside of wound[12,14].

At the beginning of the inflammatory phase, activated platelets also release pro-inflammatory cytokines and growth factors to stimulate the recruitment of immune cells to clean the wound area, initially involving infiltration of neutrophils and monocytes[15]. Monocytes undergo a phenotypic change to become macrophages. The previously constricted blood vessels also vasodilate because of increased prostaglandins, facilitating the chemotaxis of inflammatory cells[16,17]. The proliferation phase is charactered by re-epithelialization, capillary regeneration and the formation of granulation tissue(18). Fibroblasts and endothelial cells proliferate during this phase, stimulated by the numerous cytokines and growth factors released by the platelets and macrophages. This leads to the formation of new blood vessels in a process called angiogenesis[18].

After migration to the wound site, fibroblasts begin to proliferate and synthesize collagen and extracellular matrix components, such as proteoglycans, hyaluronic acid, glycosaminoglycans, and fibronectin, to form granulation tissue[1618]. The final stage is remodelling, which can last for several years. The formation of new capillaries slows, facilitating maturation of blood vessels in the wound. Type III collagen is replaced by type I collagen in the extracellular matrix to create a denser matrix with a higher tensile strength. The differentiation of fibroblasts into myofibroblasts causes the wound to physically contract. However, owing to differences in collagen type, new tissue after healing does not fully regain its original strength[1618].

Delayed wound healing can be caused by local and/or systemic factors. Local factors in the wound site include oxygen deficiency (causing chronic hypoxia), excessive exudate (causing maceration) or insufficient exudate (leading to desiccation), local infection, foreign bodies intensifying the inflammatory response, repetitive trauma, pressure/shear, and impaired vascular supply to the injury area[16,19].

Systemic factors that delay the healing process include the following[16,19]:

Oestrogen insufficiency, for instance in postmenopausal women, is known to impair all stages of wound repair process, especially inflammation and regranulation, with improved wound healing being a potential benefit of hormone replacement therapy. Androgens can repress cutaneous repair in both acute and chronic wounds, retarding the healing process and increasing inflammation[20].

The process can also be delayed in people with immunocompromised conditions, such as acquired immunodeficiency syndrome, cancer and malnutrition, with deficiencies in protein, carbohydrates, amino acids, vitamins A, C and E, zinc, iron, magnesium all having an effect[16,19,21]. Certain medicines can also delay the process, such as glucocorticoid steroids, chemotherapeutic drugs and non-steroidal anti-inflammatory drugs[19,21].

The most common causes of delayed chronic wound healing are infection and biofilm formation: biofilms are microscopically identifiable in up to 60% of chronic and recurrent wounds,leading to significant morbidity and mortality and an escalated healthcare cost[5,22,23].

A wound is considered infected when there are sufficiently large numbers of microbes presenting in wound environment or sufficient virulence to raise either a local or systemic immune response.

The wound-infection continuum has three stages: contamination, colonisation and infection. In the contamination phase, micro-organisms are unlikely to replicate because of an unfavourable environment. Colonisation happens when microbes successfully multiply, but not in sufficient levels to destroy host defences. However, the accelerated loads and persistence of microbes in wound environments may prolong the inflammatory phase and delay wound healing. When bacteria invade deeper into the wound bed and proliferate speedily, they can provoke an immune reaction and initiate local infection. As pathogens proliferate beyond the boundaries of the wound, infection may spread into deeper tissues, adjacent tissues, fascia, muscle or local organs. Eventually, systemic infection, such as sepsis, can occur when microbes invade into the body via vascular vessels or lymphatic systems, affecting the entirety of the body[24,25].

Biofilm is an extracellular polymeric substance produced by bacteria that acts as a physical barrier, enveloping bacteria and protecting them from host defences and antimicrobial agents. Several pathogens isolated from chronic wounds are typically capable of forming biofilms, such asStaphylococcus aureusandPseudomonas spp[5,23,24,26]. Biofilms persisting within chronic wounds can continuously stimulate host immunity, resulting in the prolonged release of nitric oxide, pro-inflammatory cytokines such as interleukin-1 and TNF-, and free radicals, and activation of immune complexes and complement, causing the healing process to fail and convert to a chronic state[23,27]. Sustained inflammatory reactions also trigger an escalated level of matrix metalloproteases, which can disrupt the extracellular matrix[16].

Most of the time, wound infection is diagnosed via visual inspection based on clinical signs and symptoms, including the classic signs of heat, pain, swelling, suppuration, erythema and fever. Typical characteristics of an acute infected wound are pain, erythema, swelling, purulent drainage, heat and malodour. In addition, a chronic wound may display signs of delayed healing, wound breakdown, friable granulation, epithelial bridging and pocketing in granulation tissue, increasing pain and serious odour.

Microbiological analysis of a specimen from wound cultures (using tissue biopsy or wound swab, pus collection or debrided viable tissue) is performed to identify causative microorganisms and guide the choice of antimicrobial therapy. Traditional diagnostics can be time consuming, and some organisms can be difficult to culture, so molecular techniques including DNA sequencing may help with characterising genetic markers[25]. Other laboratory markers, such as C-reactive protein, have also been used as markers and imaging techniques, such as CT scanning and autofluorescence imaging, may help with real-time diagnosis[25,28].

In clinical practice, the evaluation and identification of underlying conditions that affect wound healing are vital to optimising wound care. Accurate assessment of causes and comorbidities will inform the best course of treatment, such as compression therapy for venous leg ulcers or offloading (relief of pressure points) for people with diabetic foot ulcers[29]. The underlying pathologies of wounds are numerous and failure to address them can lead to a failure in healing[2,29].

Once any underlying conditions are identified, the wound bed should be prepared to optimise the chance of healing. A wound hygiene approach should be considered; its core principle is to remove or minimise unwanted materials, such as biofilm, devitalised tissue and foreign debris, from the wound bed to kickstart the healing process[30]. A holistic patient and wound assessment will ensure wound pathology and wound biofilm are managed simultaneously[30]. The TIME framework (tissue, infection/inflammation, moisture balance, edges) is a systematic approach to wound management[31]. Wound-bed preparation and the TIME approach should be used alongside a holistic assessment of other patient factors such as pain, nutrition and hydration[2].

Effective management of infection in chronic wounds involves the removal of necrotic tissue, debris and biofilms using debridement plus the appropriate use of antimicrobials (including topical antiseptics and systemic antibiotics)[1,32].

Antiseptics have a broad spectrum of bactericidal activity and are used externally for the purposes of eliminating bacterial colonisation, preventing infection, and potentially stimulating wound healing. They are less likely to cause antimicrobial resistance (AMR) than antibioticsand inhibit the development of microbes by disrupting cell walls and cytoplasmic membranes, denaturing proteins, and damaging bacterial DNA and RNA[5,23,33,34]. An ideal antiseptic agent should have broad-spectrum activity, a fast onset of action, long-lasting activity, be safe for healthy surrounding tissue, possess minimal allergenicity, be stable in blood and tissue protein, persistently remain within the wound bed, and potentially be active against biofilms[23,35]. Antiseptics, antimicrobial washes or surfactants can be used to clean the wound and peri-wound skin and prepare the wound bed for debridement[30].

A variety of antiseptic agents are used in clinical practice[23,34]:

Antiseptics can also be used as an adjunct to other therapies (e.g. negative pressure therapies) in treating complicated wound types(e.g.diabetic foot ulcers,venous leg ulcers and sternal wounds)[36].

All open wounds will be colonised with bacteria, but antibiotic therapy is only required for those that are clinically infected[37]. Systemic antibiotic therapy should only be considered for the treatment of cellulitis, osteomyelitis, sepsis, lymphangitis, abscess, and invasive tissue infection. Inappropriate use of systemic antibiotics may increase the risk of side effects and contributes to emergence of AMR[5]. The choice of initial therapy and the duration is frequently empirical and should take into account the type of wound, severity of infection, suspected pathogens and local AMR[38]. With severe infections, broad-spectrum antibiotics should be used against both gram-positive and gram-negative organisms, while a relatively narrow spectrum agent is enough for most mild and many moderate infections[5].

A systematic review assessed the clinical and cost-effective efficacy of systemic and topical antibiotic agents in the treatment of chronic skin wounds. The authors of the review suggested that there was insufficient evidence to support any routine use of systemic antibiotics in specific chronic wounds[39].

Appropriate and judicious use of antimicrobials must be considered when managing wounds. The use of topical antibiotics is not recommended for eliminating bacterial colonisation or wound infections because of their limited effectiveness, high risk of resistance and potential to cause contact allergy[5,35].

AMR occurs when microorganisms naturally evolve in ways that cause medicines used to treat infections to become ineffective, and these micro-organisms become resistant to most[40,41]. The misuse and overuse of antibiotics is a major cause of the emergence of AMR, via four main mechanisms[42]:

Moreover, the multicellular nature of biofilm matrix is likely to give extra protection to bacteria communities, makes them resistant to antibiotics. There are several proposed mechanisms for AMR related to biofilm: the alteration of chemical environment within biofilm, slow or inadequate diffusion of the antibiotics into the biofilm, and a differentiated biofilm subpopulation[43].

Topical antimicrobial use plays an important role when the wound is clinically infected or there is a suspected biofilm. The British Society for Antimicrobial Chemotherapy and European Wound Management Association position paper highlighted antimicrobial stewardship (AMS) a set of strategies to improve the appropriateness and minimise the adverse effects of antibiotic use as being central to wound care treatment to improving patient outcomes, reducing microbial resistance and decreasing the spread of infections caused by multidrug-resistant organisms[37]. Effective AMS avoids the use of antimicrobial therapy when not indicated while enabling the prescribing of appropriate antimicrobial interventions when they are indicated to treat infection.

The UK government has outlined a 20-year vision for reducing AMR, proposing a lower burden of infection through better treatment of resistant infections[44]. This includes the optimal use of antimicrobials and good stewardship across all sectors and appropriate use of new diagnostics, therapies, vaccines and interventions in use, combined with a full AMR research and development pipeline for antimicrobials, alternatives, diagnostics, vaccines and infection prevention across all sectors.

The use of alternatives to traditional antibiotic therapy is of huge interest for combating increasing AMR, including bacteriophage therapy, phage-encoded products, monoclonal antibodies and immunotherapy[45]. Among these, endolysins phage-encoded peptidoglycan hydrolases selectively targeting bacterial taxa have been identified as promising antimicrobial agents because of their ability to kill antimicrobial-resistant bacteria and lack of reported resistance However, challenges restrict the widespread use of endolysin therapy, such as limited drug-delivery methods, their specificity to particular bacteria types, and bioavailability via IV administration[46,47].

Debridement is the physical removal of biofilm, devitalisedtissue, debris and organic matter and is a crucial component of wound care. The presence of non-viable tissue in the wound bed prevents the formation of granulation tissue and delays the wound healing process. The removal of non-viable tissue encourages wound healing. The type of tissue found in the wound bed (e.g. whether necrotic or sloughy) will determine whether debridement is required. Factors such as bioburden, wound edges and the condition of peri-wound skin can also influence whether debridement is required[48]. A range of techniques can be used, dependent on the clinicians ability level: these include autolytic, larval, mechanical, sharp and surgical methods[49,50].

The concept of moist wound healing is not newand can lead to healing up to 23 times quicker than that of dry wound healing[51,52].Wound dressings such as cotton wool, gauze, plasters, bandages, tulle or lint should not be used, as they do not promote a moist wound healing environment, require excessive changes, and can cause skin damage and pain during dressing changes. They have therefore been replaced by newer types of wound dressingsthat can play a role in autolysis and debridement, maintain a relatively stable local temperature, keep the wound hydrated, promote wound repair and prevent bacterial infection[14,53,54].

Wound dressings should keep the wound free from infections, excessive slough, contaminants and poisons, keep the wound at the ideal temperature and optimum pH for healing, be permeable to water, but not microbes, come away from wound trauma during dressing changes, not be painful and be comfortable[55]. There are a variety of dressings available for managing chronic wounds, such as hydrogels, hydrocolloids, alginates, foams, and film dressings[56]. Dressings can also be used carriers for active agents including growth factors, antimicrobial agents, anti-inflammatory agents, monoterpenes, silver sulfadiazine or silver nanoparticles[57].

Potential factors that may influence dressing selection include:

Antimicrobial dressings impregnated with iodine, silver and honey are available[58]. They can be divided into two categories: those that release an antimicrobial into the wound and those that bind bacteria and remove them from the wound into the dressing. A more detailed overview can be found in a recent consensus document on wound care and dressing selection for pharmacists[57].

It is essential wound dressings do not inadvertently lead to moisture-associated skin damage an umbrella term encapsulating incontinence-associated dermatitis, intertriginous dermatitis (or intertrigo), peri-wound maceration and peristomal dermatitis. Practitioners should ensure the dressing can manage any exudate and protects the peri-wound area. Skin barriers can be used to protect the peri-wound area and prevent skin damage[59].

Widely used to aid the healing of acute, chronic and traumatic wounds, negative-pressure wound therapy (NPWT) removes interstitial fluid/oedema and excessive exudate, provides a moist environment, improves blood flow and tissue perfusion, and stimulates angiogenesis and granulation tissue formation[4,60]. Results from several studies have demonstrated the selective effect of NPWT in eliminating non-fermentative gram-negative bacilli in wounds[36]. Additionally, NPWT can be combined with additional topical antimicrobial solutions, reducing bacteria load, stimulating wound closure and decreasing wound size faster than conventional NPWT[36,61,62].

Hyperbaric oxygen therapy wasfirst proposed as an additional treatment for chronic wounds in the mid-1960s. Treatment involves the intermittent exposure of the body within a large chamber to 100% oxygen at a pressure between 2.0 and 2.5 atmosphere absolute, leading to an increase in oxygen levels within haemoglobin and elevating oxygen tissue tension at the wound site[63].A Cochrane reviewpublished in 2015 reported a significant improvement in the healing of diabetes ulcers in the short term when treated with hyperbaric oxygen therapy. However, further high-quality studies are needed before clinical benefits can be proven[64].

For chronic wound healing, electrical stimulation is the most frequently studied biophysical therapy[4]. It uses direct current, alternative current, and pulsed current. Electrical stimulation has been shown to benefit every stage of the wound-healing process, both at cellular and systemic levels. During the inflammation phase, electrical stimulation promotes vasodilation and increases the permeability of blood vessels, thereby facilitating cellular movement to the wound site and so promoting a shorter inflammatory response.

Studies have reported an inhibition in bacterial proliferation after electric stimulation. In the proliferation phase, electrical stimulation raises the migration, proliferation and differentiation of endothelial cells, keratinocytes, myofibroblasts and fibroblasts. At the systemic level, it promotes revascularisation, angiogenesis, collagen matrix organisation, wound contraction, and re-epithelialisation. Ultimately,electrical stimulation promotes the contractility of myofibroblast and converts type III collagen into type I, along with rearranging collagen fibres to optimise the scars tensile strength[8,65,66].

A prospective clinical study conducted across the UK suggested that using an externally applied electroceutical device, combined with compression bandaging and dressings, was a cost-effective treatment for venous leg ulcers, compared with conventional treatments[67].

Low-frequency ultrasound has been used as an adjunct treatment for chronic wounds. It has a debriding effect, removing debris and necrotic tissue (primarily via cavitational and acoustic streaming phenomena). Ultrasound is also reported to disrupt biofilmin vitro, thus increasing the sensitivity of bacteria to antimicrobials[68]. It is proposed to be effective instimulating collagen synthesis, increasing angiogenesis,diminishing the inflammatory phase as well as promoting cellular proliferation[69].Several clinical studies have shown a reduction in wound size when wounds are treated with low-frequency ultrasound therapy[7072].

Extracorporeal shock wave therapy (ESWT) has been proposed to aid wound healing by transmitting acoustic pulsed energy to tissues. ESWT seems to promote angiogenesis, stimulate circulation, reduce anti-inflammatory response, and upregulate cytokine and growth-factor reactions[4]. A clinical trial demonstrated the feasibility and tolerability of ESWT in wounds with different aetiologies[73]. Furthermore, a review concluded that ESWT brings more benefits for patients with diabetic foot ulcers than hyperbaric oxygen therapy, based on increased angiogenesis, tissue perfusion and cellular reactions with reduced cell apoptosis, as well as a higher ulcer healing rate[74].

More recent developments include introducing nanomedicine to wound-healing approaches. It has been used to achieve controlled delivery, stimulate chronic wound healing and control microbial infections[14,75]. Nanotechnology-based wound dressings like nanogels and nanofibers offer a larger surface area and greater porosity, potentially enhancing absorption of wound exudate. They can also facilitate collagen synthesis and ultimately re-epithelisation through supporting the migration and proliferation of fibroblasts and keratinocytes.

Nanomedicines also seem to aid healing through molecular and cellular pathways[75]. For example, a methacrylated gelatin (MeGel)/poly(L-lactic acid) hybrid nanofiber synthesised has been reported to stimulate the recruitment and proliferation of human dermal fibroblasts, thereby promoting wound healing[76]. Nanoparticles can not only act as carriers of antimicrobial agents, they can also have an intrinsic antimicrobial effect[75,77,78]. In 2021, Qiu et al. successfully developed an antibacterial photodynamic gold nanoparticle (AP-AuNPs) that demonstrated antibacterial effects on both Gram-negativeEscherichia coliand Gram-positiveStaphylococcus aureus,as well as potentially inhibiting biofilm formationin vitro[79].

Growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) are down-regulated in chronic wounds, suggesting that topical administration of growth factors and cytokines could improve wound healing[80].

Growth factors can improve wound repair through several mechanisms[81]:

Growth factors that have been studied in wound healing are EGF, VEGF, FGF, PDGF, transforming growth factor-beta 1 (TGF-1) and granulocyte-macrophage colony stimulating factor[82]. Becaplermin (rhPDGF-BB) was the first growth-factor therapy approved by the US Food and Drug Administration, after it demonstrated effectiveness in treating complex wounds when combined with standard wound care[80]. A systematic review and meta-analysis indicated that growth factors were effective in healing venous stasis ulcers, increasing wound healing by 48.8% compared with placebo and showing no difference in adverse effects compared with controls[83].

Stem cells may have certain advantages in wound healing because of their ability to differentiate into specialised cells and secrete numerous mediators including cytokines, chemokines, and growth factors[84,85]. This makes them a promising approach for treating chronic wounds.

Mesenchymal stem cells can be extracted from bone marrow, adipose tissue, umbilical cord blood, nerve tissue, or dermis and used both systemically and locally[86]. They release growth factors that stimulate blood-vessel and granulation tissue formation, fibroblast and keratinocyte migration, collagen synthesis, and fibroblast activation, increase re-epithelialisation, exert immunomodulatory properties, regulate inflammatory responses, and display antibacterial activities[85,8789].

Many studies have investigated the efficacy of stem-cell therapies for a variety of wounds, including burns, non-healing ulcers, and critical limb ischemia[9096]. A systematic review published in 2020 that investigated the clinical application of stem-cell therapy for the treatment of chronic wounds showed the potential of a variety of stem cells in the restoration of impaired wound healing, bothin vitroandin vivo, despite the clinical evidence being very limited. As the recorded studies were on case-by-case basis, there is a lack of comprehensive guidelines for the use of stem cells in different wounds[97].

Auto-transplantationof adipose tissue-derived mesenchymal stromal cells has been proposed as a safe, alternative method to treat chronic venous ulcers[96]. Bioscaffold matrices comprising hyaluronic acid, collagen or other bio-polymeric materials have increasingly been applied for stem-cell transplantation. These matrices not only provide wound coverage, but also offer protection for stem cells and controlled delivery[86].

Skin equivalents are polymeric biomaterials increasingly adopted for both acute and non-healing ulcers, such as venous ulcers, diabetic foot ulcers or pressure ulcers, to temporarily or permanently substitute the structure and function of human skin. Skin substitutes are designed to increase wound healing, provide a physical barrier that protects the wound from trauma or bacteria, provide a moist environment for the repair process, replace impaired skin components and decrease morbidity from more invasive treatments like skin grafting[98,99].

They can usually be classified as one of three major types: dermal replacement, epidermal replacement, and dermal/epidermal replacement[98]. Epidermal replacements (substitutes) comprising isolated autogeneous keratinocytes cultured on top of fibroblasts include Myskin (Regenerys), Laserskin(Fidia Advanced Biopolymers) and Epicel(Genzyme Tissue Repair Corporation). Dermal replacements include Dermagraft (Smith and Nephew) and Transcyte(Shire Regenerative Medicine)[98].

Epidermal/dermal skin replacements (also called composite skin substitutes) contain both epidermal and dermal layers that mimic the histological structure of original skin. The bi-layered bioengineering skin Apligraf (Organogenesis) was the first living skin equivalent for the management of complex chronic wounds like diabetic foot ulcers and venous leg ulcers. It is made up of a dermal layer of human fibroblasts embedded in a bovine type I collagen matrix and an epidermal layer generated by human keratinocytes[100]. Some other commercial products of composite substitutes are OrCel(Forticell Bioscience) andPermaDerm(Regenicin)[98]. In general, the current high cost of such dressings and limited evidence on effectiveness restricts them from being widely adopted[101]. Recently, technologies such as electrospinning or 3D-printing have been used to fabricate skin substitutes. Electrospinning can create nanofibers with high oxygen permeability, variable porosity, a large, exposed surface area and a morphology similar to the extracellular matrix, making them interesting candidates for skin substitutes[102,103].

TheNational Wound Care Strategy Programme, which was implemented by NHS England in 2018, has made progress in reducing unwanted variation in care and addressing suboptimal wound care.

Through its workstreams, the involvement of stakeholders, patients and carers, and the publication of the core capabilities for educating a multi-professional workforce, wound care has become a national priority. There are still many challenges in the management of chronic wounds the complexity of wound environment, limited knowledge of the biological, biochemical, and immunological healing processes, and the increasing complexity of disease pathophysiology that comes with ageing populations.

The development of standardised and clinically relevant testing for wound dressings, along with high-quality clinical trials, would enable useful comparisons of treatments. The whole episode of care should be considered in assessments of the cost-effectiveness of different dressings and devices, rather the simple cost of the individual entity. All these complex concerns restrict success in wound management, which in turn negatively impacts the quality of life of the patients and places a burden on global healthcare systems[75,104]. Organisations and healthcare providers should share best practice and education of healthcare professionals is needed to get the best outcomes for patients with preventable chronic wounds.

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Bhagavan N, Ha C-E. Biochemistry of hemostasis. In: Essentials of Medical Biochemistry . Academic Press 2015. 752.

13

14

15

Pratt J, West G. Pressure therapy: history and rationale. In: Pressure garments: A manual on their design and fabrication. ButterworthHeinemann 1995. 146.

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19

20

22

24

25

26

29

30

31

32

34

35

36

37

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45

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Moffatt C, Martin R, Smithdale R. Leg ulcer management. Blackwell Publishing 2007.

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Current and advanced therapies for chronic wound infection - The Pharmaceutical Journal

Cardiac Stem Cells Comments Off on Current and advanced therapies for chronic wound infection – The Pharmaceutical Journal | July 16th, 2022

Have something to say? Lookout welcomes letters to the editor, within our policies, from readers. Guidelines here.

Like many moms, UC Santa Cruz stem cell biologist Lindsay Hinck struggled to make enough milk to feed her infant daughter.

Frustrated by her low supply, she went to a lactation consultant, who advised her to wake up every night at 3 a.m. an optimal time in the hormone cycle to pump precious drops of liquid gold for her baby.

Hinck did it, but she also wondered, why was she having so much trouble and losing so much sleep while other moms had no problem feeding their newborns?

After many exhausting early hours with the pump, Hinck did what she does best: research. She found something remarkable: More than 25% of women worldwide struggle to produce enough milk to feed their infant children.

But when she looked to scientific literature for an explanation, it came up empty.

Hinck, who got a masters degree in biochemistry from UC Davis and her Ph.D. in cancer biology from Stanford University, was shocked to realize scientists have barely studied human lactation. There was almost no information for scientists or moms about how human breast tissue makes milk.

Hinck decided to change that.

She switched her UCSC labs research focus from breast cancer to lactation, specifically looking into how stem cells in breast tissue create milk and why some womens supply comes out low.

Its a topic some view with skepticism; lactation and breastfeeding are still treated by many as uncomfortable or inappropriate. In fact, in the early days of her research, Hinck had to get funding from an animal health firm interested in increasing milk production in cows.

We sexualize breasts in the most amazing ways, and people dont seem to have a problem talking about that, says Hinck, who has been at UCSC since 1998 and serves as co-director of the universitys Institute for the Biology of Stem Cells. Yet when it gets down to their biological function which is to provide nutrition for infants somehow the world clams up.

With the a nationwide baby formula shortage having affected millions of families, Hincks work funded by the National Institutes of Health takes on even greater importance. Parents whose infants have allergies or metabolic conditions rely on formula, and women particularly those who are already struggling to breastfeed cant suddenly build a milk supply overnight when formula is not available.

Hinck spoke with Lookout from her office at UCSC; this interview has been edited for clarity.

Lookout: What is lactation insufficiency?

Lindsay Hinck: Lactation insufficiency is the inability of a woman to produce the breast milk in daily volumes that meet the nutritional needs of her infant.

The statistics that we have are very broad. Somewhere between 25% and 67% of women will experience this worldwide. And this statistic is so broad because lactation insufficiency is understudied, and its hard to study.

A lot of scientists would agree that breast milk does confer an immunological advantage, and that it is filled with immune cells that the mother is giving to her infant; milk is also filled with microbes. Those are two of the major deliveries to children that come through breast milk, not to mention all the comfort of the breastfeeding cycle, psychological comfort and connectedness through the skin on skin feeling of being fed that way.

Lookout: How do you feel about your research in the context of the baby formula shortage?

Hinck: A lot of women rely on formula because they have trouble building a milk supply. Currently there are no FDA (U.S. Food and Drug Administration)-approved drugs in the United States for lactation insufficiency. My research is identifying therapeutically relevant drug targets, so that maybe we will be able to address this issue. We hope that one day women can take a drug to better build a milk supply.

Were working on a nonhormonal drug. The current drugs work on the hormone prolactin, whereas my lab studies stem cells. None of the drugs targeting prolactin have been approved, because they have terrible side effects.

Hormones have wide-ranging effects. Theyre released and they spread throughout the body. I think maybe we have an opportunity to identify a therapeutic that wont have so many deleterious side effects.

(Mel Melcon / Los Angeles Times)

Lookout: Because of the baby formula shortage, an easy answer might be to tell mothers they should just breastfeed. Why might that not be a compassionate or realistic response?

Hinck: No, thats not a compassionate or realistic response. I mean, especially if you havent built your milk supply, its not a trivial thing. If you didnt build a milk supply from the beginning, and even if you are breastfeeding, if you cant meet the daily needs of your infant, you simply dont have the milk. Its just not there.

Building a milk supply doesnt occur over 24 hours, you cant just latch the child on more often and have more milk in a day. Eventually the milk supply will increase, but its complicated. Its hard for some women to initiate and build a milk supply.

Lookout: In the U.S., lactation and breastfeeding seem to be treated as somewhat taboo or uncomfortable topics. How do you respond to that?

Hinck: We dont want to see women doing it. It seems to make people uncomfortable, so at best we provide women a room somewhere, and at worst there are no accommodations. We certainly dont appear as a society that welcomes breastfeeding in public. I am bemused at this, and find it tragic at the same time.

I myself, when I breastfed, I just breastfed. I just got to the point where tough, you know? I know I made people uncomfortable. My mother-in-law would try to drape a huge blanket over me and my child in the summer in the heat, and it was like 100 degrees underneath that blanket. I would just be like, This is crazy! Its just an infant at my breast eating. Seems fine to me. And I dont think the climate has dramatically changed in many places in the world. My daughter is 22 years old, and in 22 years I have not seen that needle budge. It still seems like breastfeeding makes people uncomfortable, and I dont know why.

Lookout: Have you faced any skepticism about this as a research topic, or faced any particular challenges in studying lactation compared to other topics, like cancer?

Hinck: I would say that I have had a harder time getting my lactation research funded. But recently, I received a NIH grant from the National Institutes for Child Health and Human Development, so thats been terrific. There has been a gaining interest in a number of whats been classified as womens diseases that have been understudied for a long time.

But in the early days, I got money from an animal health firm because they were interested in increasing milk supply in cows. The biology is the same, however. So that worked out for me, and we were able to have a project that involves looking to see if this would work for building milk supply in cows, and then we were able to unravel the basic pathways, and now were applying that.

Lookout: What would you say are the big questions driving your current research?

Hinck: How does the breast tissue know how many progenitor cells to release or recruit to expand and to build the milk supply?

Breast stem/progenitor cells have to last a whole lifetime, and they have limited potential. Theyre stemlike in that they undergo an asymmetric cell division, which is a special type of cell division that recreates the stem/progenitor cells and gives rise to daughter cells that can go on to expand and become the milk producing cells.

So how many of those asymmetric cell divisions occur? How many cells are recruited to undergo those asymmetric cell divisions? All of that is unknown. Remember, the stem cell, the progenitor cell, wants to divide as infrequently as possible. Every time they replicate their DNA, it is opening up the possibility of damage that could lead to cancer.

Lookout: How would understanding these progenitor cell pathways help improve peoples lives, or pursue a solution to lactation insufficiency?

Hinck: Its early days. We dont understand a lot, and of course giving drugs to women who are pregnant is tough. There are drugs on the market for lactation domperidone is the best medicine to build milk supply, but its not approved by the FDA in America. It has side effects, cardiac side effects.

So its not unheard of that there would be drugs that could help build a milk supply. I think that would be the ultimate goal of our research, to understand if there is any pharmacological intervention that could help.

Lookout: What do you think nursing mothers who are struggling with lactation need? What can we do as a society to support them?

Hinck: Well, in the short term, certainly make workplace rules that change the climate. I mean, even if the rules are in place, if women dont feel welcome to take the breaks to pump then it doesnt happen. I mean, we all know how that goes.

Give mothers more time off. Create more welcoming environments when they come back to work to support them and their desire to breastfeed their child.

And in the longer term, we could understand the biology of building milk supply, which is still quite mysterious in humans. What are some of the factors that may impinge on that during pregnancy or after pregnancy?

Lookout: What did you have to do in order to feed your child when you were having trouble making enough milk?

Hinck: I saw the lactation consultant and I was told to pump at 3 a.m. when prolactin levels are the highest. I would set the alarm and get up and pump every night. I was also working full time, pumping every four hours. But I could barely pump the amount of milk for the next day.

Thats a burden, you know? Its just hard to balance. Youve got an infant, and youve got this other role, but youre also providing all the food for them. It doesnt always work seamlessly, thats for sure. I went to work to do my science, and I did the best I could.

It was a lot of work. Its so much to expect of mothers. And we just dont give parents, mothers, the space and time to breastfeed at work. Its also underappreciated that there could be other people who want to breastfeed, and we need to open doors for them for non-birth moms, trans people. Why do we keep lactation in just the realm of women? I think that if we understood lactation physiology better, we could help people breastfeed.

Guanan Gmez-Van Cortright is a 2022 graduate of the UC Santa Cruz Science Communication masters program. She has written for Good Times, KQED radio and the San Jose Mercury News.

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Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don't - Lookout Santa Cruz

Cardiac Stem Cells Comments Off on Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don’t – Lookout Santa Cruz | July 16th, 2022

Stem Cells. Author manuscript; available in PMC 2020 Jul 1.

Published in final edited form as:

PMCID: PMC6658105

NIHMSID: NIHMS1024291

1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA

1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA

Author contributions:

Barbara Lukomska: Conception and design, financial support, collection and/or assembly of data, final approval of manuscript

Miroslaw Janowski: Conception and design, financial support, collection and/or assembly of data, manuscript writing, final approval of manuscript

It was shown as long as half a century ago that bone marrow is a source of not only hematopoietic stem cells, but also stem cells of mesenchymal tissues. Then the term of mesenchymal stem cells (MSCs) has been coined in early 1990s and over a decade later the criteria for defining MSCs have been released by International Society for Cellular Therapy. The easy derivation from a variety of fetal and adult tissues and not demanding cell culture conditions made MSCs an attractive research object. It was followed by the avalanche of reports from preclinical studies on potentially therapeutic properties of MSCs such as immunomodulation, trophic support and capability for a spontaneous differentiation into connective tissue cells, and differentiation into majority of cell types upon specific inductive conditions. While ontogenesis, niche and heterogeneity of MSCs are still under investigation, there is a rapid boost of attempts in clinical applications of MSCs, especially for a flood of civilization-driven conditions in so quickly aging societies in not only developed countries, but also very populous developing world. The fields of regenerative medicine and oncology are particularly extensively addressed by MSC applications, in part due to paucity of traditional therapeutic options for these highly demanding and costly conditions. There are currently almost 1000 clinical trials from entire world registered at clinicaltrials.gov and it seems that we are starting to witness the snowball effect with MSCs becoming a powerful global industry, however spectacular effects of MSCs in clinic still need to be shown.

Keywords: Mesenchymal stem cells, clinical, differentiation, immunomodulation, paracrine activity, history

Friedenstein was one of the pioneers of the theory that bone marrow is a reservoir of stem cells of mesenchymal tissues in adult organisms. It was based on his observation at the turn of the 1960s and 1970s., that ectopic transplantation of bone marrow into the kidney capsule, results not only the proliferation of bone marrow cells, but also the formation of bone [1] (). This indicated the existence in the bone marrow of a second, in addition to hematopoietic cells, stem cell population giving rise to bone precursors. Due to the ability of these cells to create osteoblasts, Friedenstein gave them the name of osteogenic stem cells. Friedenstein was also the first to isolate from bone marrow adherent fibroblast-like cells with the ability to grow rapidly in vitro in the form of clonogenic colonies (CFU-F; colony forming unit-fibroblast). These cells derived from CFU-F colonies were characterized by the ability to differentiate in vitro not only to osteocytes, but also to chondrocytes and adipocytes. After transplantation of CFU-F colonies into the recipient, they were capable of co-formation of the bone marrow micro-environment [2,3]. The term mesenchymal stem cells has been proposed by Caplan in 1991 because of their ability to differentiate into more than one type of cells that form connective tissue in many organs [4]. This name has become very popular and is currently the most commonly used, even though it raised doubts about the degree of their stemness [5]. Today, there are many substitutes in the literature for the abbreviation of MSCs, including Multipotent Stromal Cells, Marrow Stromal Cells, Mesodermal Stem Cells, Mesenchymal Stromal Cells and many more. In its latest work, Caplan recommends renaming these cells to Medicinal Signaling Cells due to the emphasis on the mechanism of their therapeutic effects after transplantation, which is believed to be based mainly on the secretion of factors facilitating regenerative processes [6].

The roots of research on bone marrow-derived stem cells of connective tissue, which has been then named: mesenchymal stem cells

Due to the growing controversy regarding the nomenclature, the degree of stemness and the characteristics of the cells discovered by Friedenstein, the International Society for Cellular Therapy (ISCT) in 2006 published its position specifying the criteria defining the population of MSCs, which was accepted by the global scientific community. These guidelines recommend the use of the name multipotent mesenchymal stromal cells, however, the name mesenchymal stem cells still remains the most-used. The condition for the identification of MSCs is the growth of cells in vitro as a population adhering to the substrate, as well as in the case of cells of human origin, a phenotype characterized by the presence of CD73, CD90, CD105 surface antigens and the lack of expression of proteins such as: CD45, CD34, CD14, CD11b, CD79a or CD19 or class II histocompatibility complex antigens (HLA II, human leukocyte antigens class II). Moreover, these cells must have the ability to differentiate towards osteoblasts, adipocytes and chondroblasts [7,8]. In addition to the markers mentioned in the ISCT guidelines, the following antigens turned out to be useful in isolating the human MSCs from the bone marrow: STRO-1 (antigen of the bone marrow stromal-1 antigen, cell surface antigen expressed by stromal elements in human bone marrow-1), VCAM / CD106 (vascular cell adhesion molecule 1) and MCAM / CD146 (melanoma cell adhesion molecule), which characterizes cells growing in vitro in a adherent form, with a high degree of clonogenicity and multidirectional differentiation ability [911].

The common mesenchymal core in both versions of MSC abbreviation comes from the term mesenchyme, which is synonymous with mesenchymal tissue or embryonic connective tissue. It is used to refer to a group of cells present only in the developing embryo derived mainly from the third germ layer - mesoderm. During the development these cells migrate and diffuse throughout the body of the embryo. They give rise to cells that build connective tissue in adult organisms, such as bones, cartilage, tendons, ligaments, muscles and bone marrow. The view about the differentiation of MSCs during embryonic development from mesenchymal cells is widely spread [4]. This is due, inter alia, to the observed convergence in the expression of markers such as: vimentin, laminin 1, fibronectin and osteopontin, which are typical for mesoderm cells during embryonic development, as well as characteristic for in vitro adherent bone marrow stroma cells [12]. However, the true origin of MSCs is unknown. In the literature, we can find also reports indicating that they are ontogenetically associated with a group of cells derived from ectoderm, which originate from Sox1 + cells (SRY - sex determining region Y) that appear during the development of embryonic neuroectoderm and neural crest. These cells inhabit newborn bone marrow and meet the criteria corresponding to their designation as MSCs. However, with the development of animals, the population of these cells disappears and is replaced by cells with a different, unidentified origin [13]. It has also been shown that in the bone marrow of the developing mouse embryo, at least two MSCs populations with distinct expression of the nestin protein and the intensity of cell divisions can be distinguished. The former one originates from mesoderm that does not express nestin, and is characterized by intense proliferation and is involved in the process of creating the embryo skeleton. The latter one is derived from the cells of the neural crest, which expresses nestin and is non-dividing and remains passive during bone formation while in the adult organism contributes to a niche of hematopoietic cells [14]. It seems, therefore, that the ontogenesis of MSCs is associated with cells belonging to different germ layers and their original source determines the role and functions that they play in the adult body.

In 1978, the concept of a niche was defined as a place in the body that is settled by stem cells and whose environment allows them to be maintained in an undifferentiated state [15]. MSCs were first obtained from the bone marrow stroma where they constitute an element of stromal cells, participating in the production of signals modulating the maturation of hematopoietic cells. However, the precise location of the niche for MSCs has not been known so far. In the context of research results indicating that MSCs can be isolated from many mesoderm-derived tissues during embryonic development, a common element was sought for all sources from which MSCs can be isolated and a theory was proposed about the existence of their niche within the blood vessels that are present in all structures from which these cells were isolated.

Crisan and colleagues have shown that cells inhabiting the perivascular space of blood vessels, isolated from human tissues such as skeletal muscle, pancreas, adipose tissue and placenta, with the phenotype CD146 +, NG2 + (neuroglycan-2), PDGF-R + (-type platelet-derived growth factor receptor), ALP + expressing endothelial, hematopoietic and muscle cell markers described as pericytes were precursors for cells that after in vitro expansion meet the criteria for determining them as MSCs [16]. Analogously to the described by Friedenstein MSCs, CD146 + cells colonizing the perivascular space of sinusoidal sinus vessels, are responsible for the production of signals allowing the reconstruction of the bone marrow microenvironment after transplantation to heterotopic location [11]. Whats more, tracing the fate of pericytes in the process of rebuilding a damaged tooth in rodents has shown that they are transforming into odontoblasts, which arise from MSCs found in the pulp. However, the same studies showed that in the process of reconstruction of incisors in mice, a different population of odontoblasts, which is not formed from pericytes, but from MSCs of different origin migrating to the area of damage, prevailed quantitatively [17]. The second cell population associated with blood vessels, proposed as a counterpart of MSCs in the body is advent building cells with the CD34+ CD31- CD146- phenotype, which after isolation and in vitro culture meet the criteria defining the population as MSCs. However, these cells also have the ability to differentiate into pericytes [18,19]. Although pericytes and MSCs have a very similar gene expression profile as well as an analogical capacity for differentiation, it has been shown that the functionality of these cells varies. In vitro studies of endothelial cell interactions in co-culture with MSCs or pericytes have shown that only pericytes are able to form highly branched, dense, cylindrical structures with large diameter, typical for well-organized blood vessels, while isolated from the bone marrow MSCs do not have such abilities. Currently, it is believed that there is a link between pericytes and MSCs, but their mutual relations are not well defined. There are speculations that MSCs are an intermediate form of pericytes or their subpopulation, but there is still no conclusive evidence confirming this hypothesis [20,21].

While the cells fulfilling criteria for MSCs can be harvested from various tissues at all developmental stages (fetal, young, adult and aged) using their plastic adherence property, there are profound differences between obtained MSC populations [22,23]. Bone marrow was historically the first source from which MSCs were obtained, however, over time, there have been reports of the possibility of isolation from other sources of cells with similar properties. Mesenchymal cells are obtained from both tissues and secretions of the adult body, such as adipose tissue, peripheral blood, dental pulp, yellow ligament, menstrual blood, endometrium, milk from mothers, as well as fetal tissues: amniotic fluid, membranes, chorionic villi, placenta, umbilical cord, Wharton jelly, and umbilical cord blood [2437]. MSCs of fetal origin as compared to cells isolated from tissues of adult organisms are characterized by a faster rate of proliferation as well as a greater number of in vitro passages until senescence [38]. However, MSCs derived from bone marrow and adipose tissue are able to create a larger number of CFU-F colonies, which indirectly indicates a higher degree of their stemness. The comparison of gene expression typical for pluripotent cells shows that only in cells isolated from the bone marrow we can observe the expression of the SOX2 gene, the activation of which is associated with the self-renewal process of stem cells as well as with neurogenesis during embryonic development [39]. Discrepancies in the ability of MSCs obtained from various sources to differentiate have also been described. The lack of differentiation of MSCs derived from umbilical cord blood towards adipocytes as well as the greater tendency of MSCs from bone marrow and adipose tissue to differentiate towards osteoblasts were observed [39,40].

In addition to the diverseness observed between MSCs from different sources, there are also differences associated with obtaining them from individual donors. Among the cells isolated from the bone marrow from donors of different ages and sexes, up to 12-fold differences in the rate of their proliferation and osteogenesis were found, combined with a 40-fold difference in the level of bone remodeling marker activity - ALP (alkaline phosphatase). At the same time, no correlations were found resulting from differences in the sex or age of donors [41]. However, the results of studies by other authors indicate that the properties of MSCs isolated from the bone marrow are strongly associated with the age of the donor. Cells collected from older donors are characterized by an increased percentage of apoptotic cells and slower rate of proliferation, which is associated with an increased population doubling time. There is also a weakened ability of MSCs from older donors to differentiate towards osteoblasts [42]. Heo in his work shows the different ability of MSCs to osteogenesis combining it with different levels of DLX5 gene expression (transcription factor with the homeodomain 5 motif) in individual donors, however independent of the type of tissue from which the cells were isolated [39].

The next stage in which we can observe diversity among the MSCs population is in vitro culture. The morphology of cultured cells that originate from the same isolation allows for differentiation into three sub-populations. There are observed spindle-shaped proliferating cells resembling fibroblasts (type I); large, flat cells with a clearly marked cytoskeleton structure, containing a number of granules (type II) and small, round cells with high self-renewal capacity [43,44]. The original hypothesis assumed that all cells that make up the MSCs population are multipotent, and each colony of CFU is capable of differentiating into adipocytes, chondrocytes and osteoblasts, as confirmed by appropriate studies [45]. However, in the literature we can find reports that cell lines derived from a common colony of CFU-F differ in their properties, characterized by uni-, di- or multipotence [46]. Some of the authors showed the division of clonogenic MSCs colonies into as much as eight groups distinct in their potential for differentiation. At the same time, it is suggested that there is a hierarchy within which cells subordinate to each other are increasingly directed towards osteo- chondro- or adipocytes and gradually lose their multipotential properties to di- and unipotential ones. This transformation may also be associated with a decrease in the rate of cell proliferation and the level of CD146 protein expression (CD; cluster of differentiation) - proposed as a marker of multipotency [47].

One of the main advantages of MSCs are their immunomodulatory properties. MSCs grown in vitro have the ability to interact and regulate the function of the majority of effector cells involved in the processes of primary and acquired immune response () [48]. They exert their immunomodulatory effects by inhibiting the complement-mediated effects of peripheral blood mononuclear cell proliferation [49,50], blocking apoptosis of native and activated neutrophils, as well as reducing the number of neutrophils binding to vascular endothelial cells, limiting the mobilization of these cells to the area of damage [51,52]. In addition, cytokines synthesized by activated MSCs stimulate neutrophil chemotaxis and secretion of pro-inflammatory chemokines involved in recruitment and stimulation of phagocytic macrophage properties [53]. Moreover MSCs limit mast cell degranulation, secretion of pro-inflammatory cytokines by these cells as well as their migration towards the chemotactic factors [54]. Native MSCs have the ability to block the proliferation of de novo-induced NK cells, but they are only able to partially inhibit the proliferation of already activated cells [55]. They also contribute to the reduction of cytotoxic activity of NK cells [56]. Moreover MSCs can block the differentiation of CD34 + cells isolated from the bone marrow or blood monocytes into mature dendritic cells both by direct contact as well as by secreted paracrine factors [57,58]. They inhibit the transformation of immature dendritic cells into mature forms and limit the mobilization of dendritic cells to the tissues [59]. Under their influence, M1 (pro-inflammatory) macrophages are transformed into M2 type cells with an anti-inflammatory phenotype, and the IL-10 (IL, interleukin) secreted by them inhibits T-cell proliferation [60,61]. In vitro studies have demonstrated a direct immunomodulatory effect of MSCs on lymphocytes. During the co-culture of MSCs with lymphocytes, suppression of activated CD4 + and CD8 + T cells and B lymphocytes was observed [62]. In addition, MSCs reduce the level of pro-inflammatory cytokines synthesized by T-lymphocytes, such as TNF- (tumor necrosis factor ) and IFN- (interferon ) [63], and increase synthesis of anti-inflammatory cytokines, e.g. IL-4. In the presence of MSCs, the inhibition of the differentiation of naive CD4 + T lymphocytes to Th17 + lymphocytes (Th; T helper cells) was observed, while the percentage of T cells differentiating towards CD4 + CD25 + regulatory T cells was found to increase [64,65]. Glennie et al. described this condition as anergy of activated T cells in the presence of MSCs [62]. MSCs also have the ability to limit the synthesis of immunoglobulins like IgM, IgG and IgA (Ig; immunoglobulin) classes secreted by activated B cells, thereby blocking the differentiation of these cells to plasma cells. They also reduce the expression of chemokines and their receptors on the surface of B lymphocytes, which probably have a negative effect on their ability to migrate [66].

The schematic representation of immunomodulatory capabilities of MSCs

Mesenchymal stem cells secrete a wide range of paracrine factors, collectively referred to as the secretome, which support regenerative processes in damaged tissues. They comprise the components of the extracellular matrix, proteins involved in the adhesion process, enzymes as well as their activators and inhibitors, growth factors and binding proteins, cytokines and chemokines, and probably many more [67]. These factors can have distinct impact on the processes they regulate (). MSCs secrete factors promoting angiogenesis, such as: vascular endothelial growth factor (VEGF) but they may also inhibit this process, through expression of monokine induced by interferon and tissue inhibitors of metalloproteinases 1 and 2 [68,69]. An important role is also played by chemokines secreted by MSCs in the process of blocking or stimulating cell chemotaxis, such as: CCL5 (RANTES, regulated by activation, expression and secretion by normal T lymphocytes), CXCL12 (SDF-1, stromal cell-derived factor 1) or CCL8 (MCP-2; monocyte chemoattractant protein 2). An essential group of factors from the point of view of regeneration processes are growth factors with an anti-apoptotic effect, including: HGF (hepatocyte growth factor), IGF-1 (insulin-like growth factor 1), VEGF, CINC-3 (cytokine induced by a chemoattractant for neutrophil chemoattractant), TIMP-1 (tissue inhibitor of metalloproteinases 1), TIMP-2 (tissue inhibitor of metalloproteinases 2), osteopontin, growth hormone, FGF-BP (bFGF binding protein), and BDNF (brain-derived growth factor; -derived neurotrophic factor) and stimulating proliferation as: TGF- (transforming growth factor ), HGF, EGF (epidermal growth factor), NGF (nerve growth factor; nerve growth factor), bFGF (basic fibroblast growth factor), IGFBP-1, IGFBP-2 (IGFBP; insulin-like growth factor 1 binding protein, IGF-Protein-1 protein) and M-CSF (stimulant factor t molar macrophage colony; macrophage colony-stimulating factor) [68,70,71]. Growth factors secreted by MSCs have also ability to reduce fibrosis of tissues during regeneration. These include KGF (keratinocyte growth factor), HGF, VEGF, and Ang-1 (angiopoietin-1), SDF1, IGF-1, EGF, HGF, NGF, TGF- [71,72]. There are reports about the antibacterial properties and interaction of the MSC secretome with cancer cells. Data on the impact of MSCs on neoplasia are not conclusive, however, it is assumed that both the tumor type and the origin of MSCs are of great importance for the final effect [73]. It was shown that factors enclosed within the MSCs secretome are able to reduce the proliferation, viability and migration of certain types of cancer cells (such as non-small-cell lung carcinoma) [74]. Others have shown that factors released by MSCs may increase motility, invasiveness and the ability to form metastases (including, for example, breast cancer cells) [75]. In response to bacteria, levels of cytokines such as IL- 6, IL-8, CCL5, PGE2, TNF-, IL-1, IL-10, VEGF and SDF-1 secreted by MSCs are subject to change [76]. MSCs contain also substances with antibacterial, anti-parasitic and antiviral activity [77].

The mechanisms mediating MSC-dependent trophic support

Another broad and dynamically developing field in recent years which is related to paracrine MSCs activity is their ability to secrete extracellular vesicles (EVs), which include exosomes, microvesicles and apoptotic bodies. Their composition largely coincides with the components contained in the cells from which they originate. Physiologically they play an important role in the regulation of biological functions, homeostasis and the immune response of the body. It is also postulated that the biological activity of microvesicles is comparable to that of MSCs [78]. Experiments conducted using supernatant derived from in vitro culture of MSCs showed that the factors contained in their secretome are responsible for a large part of the effects exerted by MSCs during the regeneration of the damaged area including the protection of other cells against apoptosis, induction of their proliferation, prevention of excessive fibrosis of tissues, stimulation of the angiogenesis process and immunomodulatory effects, as well as the induction of endogenous stem cells differentiation [65,68,69,7982].

As mentioned above, the ability to differentiate into three types of cells such as: osteocytes, chondrocytes and adipocytes is one of the criterion for MSCs [8]. This phenomenon can be traced in vitro by placing MSCs in a medium containing specific supplements, for the adipogenesis process they are mainly dexamethasone, indomethacin, insulin and isobutylmethylxanthin [83], for chondrogenesis cell culture in DMEM medium (Dulbecco / Vogt Modified Eagles Minimal Essential Medium) supplemented with insulin, transferrin, selenium, linoleic acid, selenium acid, pyruvate, ascorbic phosphate, dexamethasone and TGF- III [84], which may additionally be aided by the addition of IGF-1 and BMP-2 (BMP; bone morphogenetic proteins) [85]. In turn the osteogenesis is induced by the presence of ascorbic acid, -glycerophosphate and dexamethasone [86]. Differentiation of MSCs in the appropriate cell type is assessed by identifying the production of respectively: fat droplets (adipogenesis), proteoglycans and type II collagen synthesis (chondrogenesis) or mineralization of calcium deposits and the increase of alkaline phosphatase expression (osteogenesis). However, many literature reports indicate that by the treatment with appropriate factors MSCs might be also a source of other cell types. Caplan and Dennis in their work from 2006 present a process that they call mesengenesis, in which MSCs give also rise to myoblasts, bone marrow stromal cells, fibroblasts, cells co-creating connective tissue of the body as well as ligaments and tendons [87]. Addition of 5-azacytidine to MSCs allows to obtain muscle cells, including cardiomyocytes and myoblasts having the ability to create multinucleated miotubes and expressing markers such as: -myosin heavy chain, -actin cardiac form and desmin [88]. In addition, in vitro studies have made it possible to obtain from MSCs at least two types of cells derived from the endoderm through their transdifferentiation into hepatocytes and -cells of pancreatic islets. The liver cells are obtained from MSCs in two stages by culturing them in modified Dulbeccos medium supplemented with EGF, bFGF and nicotinamide, and in the next stage with the addition of oncostatin M, dexamethasone, insulin, transferrin and selenium. The resulting cells show the presence of markers typical for hepatocytes such as albumin, -fetoprotein and hepatocyte nuclear factor 4 (HNF-4) [89]. By the treatment with a mixture of growth factors secreted by regenerating cells of the pancreas as well as by the use of acitin A, sodium butyrate, taurine and nicotinamide the pancreatic islets of -cells capable of producing insulin were obtained from MSCs [90,91]. It has also been shown that stimulation with appropriate factors may result in the differentiation of MSCs into cells derived ontogenetically from ectoderm, such as neurons. The use of BME stimulation in vitro (-mercaptoethanol) followed by NGF leads to the differentiation of MSCs into cholinergic nerve cells expressing their typical proteins such as NF-68 neurofilaments (68 kDa Neurofilament protein with 68 kDa molecular mass), NF-200 (neurofilament protein with a molecular weight 200kDa, 200kDa neurofilament protein), NF-160 (neurofilament protein molecular weight 160kDa, 160kDa neurofilament protein), choline acetyltransferase and synapsin I [92]. Other factors mentioned as compounds inducing the transformation of MSCs into nerve cells are insulin, retinoic acid, bFGF, EGF, valproic acid, BME and hydrocortisol [93]. In addition, GNDF (glial cell-derived neurotrophic factor), BDNF (brain-derived neurotrophic factor), retinoic acid, 5-azacytidine, isobutylmethylxanthine and indomethacin stimulate the transformation of MSCs into mature neurons that express markers of nervous systems cells such as: nestin, -III tubulin, microtubule associated protein - MAP2 (microtubule associated protein 2) and neuron-specific enolase (ENO2; enolase 2) [94]. These studies show that under strictly controlled conditions prevailing during in vitro culture, in the presence of chemicals and growth factors, MSCs are able to turn into cells derived from all three embryonic germ layers ().

The differentiation potential of MSCs

It has been more than half a century since the curiosity has been revealed that not only hematopoietic cells, but also those capable of forming connective tissue reside in the bone marrow. Subsequent studies have begun to reveal the increasingly fascinating properties of these cells, which go far beyond forming connective tissue. This, combined with their easy derivation from various tissues, made them an attractive research object. Immunomodulatory properties, aiding repair of various tissues as well as differentiation potential to practically any types of cells stunned a whole host of scientists and established MSCs as a driving force of regenerative medicine and began also to play an increasingly important role in oncology [95]. We are currently observing a flood of clinical trials with the use of MSCs, and their number doubles every few years and currently reaches almost 1000 registered items on the clinicaltrials.gov website.

MSCs compose a negligible fraction of cells derived from in vivo tissues and there is no effective method to capture them directly. Therefore, MSCs need to be subjected to the process of in vitro expansion, which in clinical context is called biomanufacturing and biobanking and both terms are frequently used interchangeably to describe the process from procurement of cell source to deliver cells to the patients bed. The processing of MSCs must be performed according to current Good Manufacturing Practice (cGMP) as any other therapeutic agent and is subjected to extensive regulatory effort. Food and Drug Administration (FDA) is the main authority responsible for acceptance of medical products including those containing living cells such as MSCs in the USA. FDA has issued a perspective on MSC-based product characterization [96] and up-dated it in FDA Grand Round delivered by Steven Bauer, PhD, Chief of Cell and Tissue Therapies Branch at FDA on March 08, 2018. Both sources are an excellent overview of regulatory challenges related to the biobanking of MSCs. In general, any new product must obtain investigational new drug status (INDs) to be used in clinical trial before filing application for marketing, and there were 66 INDs submitted to FDA between 2006 and 2012. Based on that FDA engaged into regulatory research project called MSC consortium to characterize MSC based-products with an output of 16 research papers. The main organ responsible for the regulation of medical market in all Member States is European Medicines Agency (EMA) consisting of seven smaller committees. The MSCs-containing products should be classified as Advanced Therapy Medical Product (ATMP) and in detail considered as Somatic Cell Therapy Medicinal Product (CTMP) [97]. Its release on medical market has to be first accredited by Committee for Advanced Therapies (CAT) which creates the general opinion and evaluates the quality, safety and efficiency of the product. After CAT assessment the final acceptance should be then approved by Committee for the Medicinal Products for Human Use (CHMP). This type of legalization is called Centralized Marketing Authorization and it allows to use ATMP products in all European Union countries. Currently, there is a variety of protocols used for biomanufacturing and biobanking of MSCs, and once the successful stories become strong, the landscape of MSC production will probably solidify with predicted reduction of MSC production approaches due to economic and regulatory pressures.

Summing up, it seems that the MSCs are becoming a powerful global industry, ready to respond to the unmet needs of modern medicine struggling with the proper care and quality of life of rapidly aging societies, which is already affecting not only developed countries, but also very populous developing countries. In conclusion, we are beginning to observe the effect of the snowball in which ever new discoveries related to MSC are increasingly stimulating clinical applications of the MSC, which is beginning to contribute to the transformation of medical care.

Significance Statement

The research on bone marrow-derived stem cells of connective tissue is evolving and continuously expanding with a recent boost of interest in clinical applications reflected by an avalanche of nearly 1000 registered clinical trials. While, the current name: mesenchymal stem cells (MSCs) have been coined as late as early 90-ies, it is important to commemorate of the fiftieth anniversary of research on them and provide a big picture from roots of first paper in 1968, through identification of their various potential therapeutic activities such as immunomodulation, trophic support and capability for differentiation and taking role in cell replacement strategies.

This work was funded by NCR&D grant EXPLORE ME within the STRATEGMED I program and by NIH R01 NS091100-01A1.

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Mesenchymal stem cells: from roots to boost - PMC

Cardiac Stem Cells Comments Off on Mesenchymal stem cells: from roots to boost – PMC | July 8th, 2022

Lab-grown human heart cells provide a powerful tool to understand and potentially treat heart disease. However, the methods to produce human heart cells from pluripotent stem cells are not optimal. Fortunately, a new study out of the University of WisconsinMadison Stem Cell & Regenerative Medicine Center is providing key insight that will aid researchers in growing cardiac cells from stem cells.

The research, published recently in eLife, investigates the role of extracellular matrix (ECM) proteins in the generation of heart cells derived from human pluripotent stem cells (hPSCs). The ECM fills the space between cells, providing structural support and regulating formation of tissues and organs. With a better understanding of ECM and its impact on heart development, researchers will be able to more effectively develop heart muscle cells, called cardiomyocytes, that could be useful for cardiac repair, regeneration and cell therapy.

How the ECM impacts the generation of hPSC-cardiomyocytes has been largely overlooked, says Jianhua Zhang, a senior scientist at the Stem Cell and Regenerative Medicine Center. The better we understand how the soluble factors as well as the ECM proteins work in the cell culture and differentiation, the closer we get to our goals.

Researchers like Zhang have been looking to improve the differentiation of hPSCs into cardiomyocytes, or the ability to take hPSCs, which can self-renew indefinitely in culture while maintaining the ability to become almost any cell type in the human body and turn them into heart muscle cells. To investigate the role of the ECM in promoting this cardiac differentiation of hPSCs, Zhang tested a variety of proteins to see how they impacted stem cell growth and differentiation specifically, ECM proteins including laminin-111, laminin-521, fibronectin and collagen.

Our study showed ECM proteins play significant roles in the hPSC adhesion, growth, and cardiac differentiation. And fibronectin plays an essential role and is indispensable in hPSC cardiac differentiation, says Zhang. By understanding the roles of ECM, this study will help to develop more robust methods and protocols for generation of hPSC-CMs. Furthermore, this study not only helps in the field for cardiac differentiation, but also other lineage differentiation as well.

While the new study provides important insight into heart cell development, it is built upon a 2012 study Zhang led which looked at the most efficient way to develop cardiac differentiation of stem cells.

This study is actually a follow-up paper to the Matrix Sandwich Method that we developed for efficient cardiac differentiation of hPSCs, Zhang says. In order to culture the stem cells, we needed to have an ECM layer on the bottom of the plate. Otherwise, the stem cells would not attach to the plate. We would then add another layer of ECM on top of the growing stem cells, and we found that this helped promote the most effective differentiation.

While it was clear that this layering, or sandwich, method more efficiently and reproducibly differentiated hPSC-cardiomyocytes, researchers did not fully understand why. The new study explains why the ECM layers are crucial and identifies fibronectin as a key ECM protein in the development of hPSC-cardiomyocytes.

The most exciting part of this study is now I understand why the Matrix Sandwich Method worked. We were able to identify the fibronectin and its integrin receptors as well as the downstream signaling pathways in this study, Zhang explains. With a better understanding of ECMs roles in stem cell growth and cardiac differentiation, we now hope to investigate the roles of fibronectin and other ECM proteins in promoting the hPSC-cardiomyocytes transplantation for cell therapy.

The next step could help researchers realize the full potential of using hPSC-cardiomyocytes for disease modeling, drug screening, cardiac regeneration and cell therapy. This is very meaningful to Zhang, who began working in cardiovascular research more than 16 years ago.

I became interested in stem cell and heart research when I began working with the stem cells and saw them turning into heart cells beating in a cell culture dish under a microscope, Zhang says. It was amazing. Ive become more and more dedicated to this research, and I can really see the potential of using the stem cell technologies to cure disease and improve our health.

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New study allows researchers to more efficiently form human heart cells from stem cells - University of Wisconsin-Madison

Cardiac Stem Cells Comments Off on New study allows researchers to more efficiently form human heart cells from stem cells – University of Wisconsin-Madison | July 8th, 2022

He called his wife Ann once in the driver's seat to continue the conversation they'd been having over breakfast.

As he made his way towards Mosman in the usual Sydney traffic, a beat-up Toyota Corona was in the queue directly behind him.

At the intersection of Bardwell Rd and Military Rd, the Corona deliberately swerved into Dr Chang's car and so the two cars pulled over on the side of the road.

It was 8am when Phillip Lim and Chiew Seng Liew - the occupants of the Corona - pulled a pistol on Chang.

They wanted money. Lim planned to extort $3 million from a wealthy Asian businessman living in Australia, so he could set up a gambling den or massage parlour. They'd picked Dr Chang after seeing an article about him in a magazine.

Dr Chang pulled out his wallet immediately, but there were numerous witnesses watching on in horror.

Mosman Collectivequotes Chang as yelling out to someone, "call the police, theyve got guns."

He was shot twice - once in the head, once in the stomach. He died at the scene.

Liew was sentenced to a maximum of 26 years in prison for firing the two shots that killed Dr Chang. After 21 years, he was released and deported back to his home country of Malaysia in 2012.

As The Sydney Morning Heraldreported, it was a decision that "devastated" Dr Chang's family.

"I made a mistake," Liew told the Sevennetwork upon his release. "I did the wrong thing and made the family suffer ... You know I want to apologise for the family."

His co-accused Lim was granted parole after serving his minimum 18-year sentence, which expired in 2009.

Hailed as a "medical genius," Dr Chang was celebrated and admired around the world.

While he personallysaved hundreds of lives, he always had his eye on millions - which could be achieved through medical research.

After his death, the Victor Chang Foundation created by Dr Chang in 1984 with the aim of sharing expertise between Australia and Asia through training in the fields of cardiothoracic surgery, heart and lung transplantation and cardiology, continued on with his work.

But his dream was carried forward even further,with the establishment of The Victor Chang Cardiac Research Institute in 1994. It was opened by Princess Dianawho told those gathered, "Dr Chang was no ordinary cardiac surgeon. He was a visionary."

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Dr Victor Chang saved hundreds of lives. 31 years ago today, he was murdered. - Mamamia

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Wilmington, Delaware, United States, Transparency Market Research Inc.: Cell line development is an important technology in life sciences. Stable cell lines are used for various applications including monoclonal antibody and recombinant protein productions, gene functional studies, and drug screening

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Manual screening method is a traditional method used for cell line development. This method is tend to be disadvantageous as it is labor-intensive and time-consuming. Automation in tools used for cell line development is likely to replace manual methods of cell line development.

Cell line development and culturing is being rapidly adopted in areas of biological drug developments for various chronic diseases, regenerative medicines such as stem cells & cell-based therapies, recombinant protein, and other cellular entities for pharmaceuticals, diagnostics, and various other industries.

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Key Drivers and Opportunities of Global Cell Line Development Market

Rise in focus on research & development, owing to increase in prevalence of cancer and other chronic diseases is anticipated to drive the market. Several institutes, such as Cancer Research Institute, National Cancer Institute, Advanced Centre for Treatment, Research and Education in Cancer (Cancer Research Centre [ICRC]), and NCI Community Oncology Research Program (NCORP), are engaged in research & development for cancer diagnosis and treatment. Hence, the initiative of government and non-government organizations is likely boost the growth of the market.

Mammalian cell lines are widely used as production tools for various biologic drugs. Technological advancement in cell line development in mammalian cell culturing is likely to fuel the growth of the market. For instance, according to an article published in Pharmaceuticals (Basel), the U.S. Food and Drug Administered approved 15 novel recombinant protein therapeutics from 2005 to 2011 on an average.

Advances in bioinformatics and recombinant technologies have led to development of new cell lines for synthesis or production of essential peptides, enzymes, saccharides, and other molecules which are being used in pharmaceuticals and various other industries.

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North America to Capture Major Share of Global Cell Line Development Market

North America is expected to account for major share of the global cell line development market due to well-established health care infrastructure and rise in government initiatives. Furthermore, adoption of innovative technologies is likely to augment the market in the region.

The cell line development market in Asia Pacific is expected to grow at a rapid pace during the forecast period, owing to increasing risk of communicable diseases, cancer, and chronic & rare diseases and surge in geriatric population. For instance, according to an article published in BioMed Central Ltd, in 2018, 2.9 million cancer deaths occurred and 4.3 million new cancer cases were recorded in China.

Key Players Operating in Global Cell Line Development Market

The global cell line development market is highly concentrated due to the presence of key players. A large number of manufacturers hold major share in their respective regions. Key players engaged in adopting new strategies are likely to drive the global cell line development market. Key players are developing new, cost-effective biologic products. This is anticipated to augment the market.

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Major players operating in the global cell line development market are:

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Cell Line Development Market: Increase in Prevalence of Cancer and Other Chronic Diseases to Drive the Market - BioSpace

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Get PDF Sample on this Market @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-exosome-therapeutic-market&Raj

The global exosome therapeutics market competitive landscape provides details by a competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, production sites and facilities, company strengths and weaknesses, product launch, product trials pipelines, product approvals, patents, product width, and breadth, application dominance, technology lifeline curve. The above data points provided are only related to the companys focus related to the exosome therapeutics market.

For instance,

Collaboration, joint ventures, and other strategies by the market player are enhancing the company market in the global exosome therapeutics market, which also provides the benefit for an organization to improve their offering for treatment products.

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Some of the major companies influencing this market include:

Some of the major companies providing the global exosome therapeutics market are Stem Cells Group, Exosome Sciences, AEGLE Therapeutics, Capricor Therapeutics, Avalon Globocare Corp, CODIAK, Kimera Labs, Stem Cell Medicine Ltd, Exopharm, Jazz Pharmaceuticals, Inc., evox THERAPEUTICS, ReNeuron Group plc, and EV Therapeutics, among others.

Market Segmentation:-

The global exosome therapeutics market is segmented on the basis of type, source, therapy, transporting capacity, application, route of administration, and end user. The growth among segments helps you analyze niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

The global exosome therapeutics market is categorized into seven notable segments which are based on type, source, therapy, transporting capacity, application, route of administration, and end user.

Regions Covered in Artificial Intelligence in Genomics 2022 Global Market Report:

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Key questions answered in the report include:who are the key market players in the this Market?Which are the major regions for dissimilar trades that are expected to eyewitness astonishing growth for the this Market?What are the regional growth trends and the leading revenue-generating regions for the this Market?What will be the market size and the growth rate by the end of the forecast period?What are the key this Market trends impacting the growth of the market?What are the major Product Types of this Market?What are the major applications of this Market?

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Exosome Therapeutics Market Research Report Size, Share, New Trends and Opportunity, Competitive Analysis and Future Forecast Designer Women -...

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Homology Medicines, Inc.

AAVHSC16 Biodistribution Properties in Preclinical Models Demonstrated Potential for Systemic Delivery of Genetic Medicines to Brain, Heart and Muscle

BEDFORD, Mass., July 05, 2022 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the peer-reviewed publication of data showing that AAVHSC16, one of the capsids in its family of 15 naturally occurring AAVHSCs, demonstrated low levels of tropism to the liver while maintaining robust distribution to the central nervous system (CNS) and peripheral organs following a single I.V. administration in preclinical models. The Company believes that its unique properties, with high levels of tropism to the brain, heart and muscle, and no elevations in liver enzymes, could make AAVHSC16 an attractive capsid for new disease indications with Homologys genetic medicines platform.

Our ongoing efforts to fully characterize our family of 15 naturally occurring AAVHSCs as it relates to biodistribution, tissue tropism and the role different features of the capsids play, continues to reveal their unique profiles that allow us to best select capsids for different diseases, said Albert Seymour, Ph.D., President and Chief Scientific Officer of Homology Medicines. In the case of AAVHSC16 with its ability to reach key tissues without targeting the liver in preclinical models, we can potentially expand into additional disease areas where we want to deliver to the CNS, cardiac tissue, or muscle while avoiding exposure in the liver. By continuing to publish our discoveries about the unique structure and function of our AAVHSCs, we believe we can contribute to the fields greater understanding and development of AAV-based therapies that will ultimately benefit more patients.

Homologys AAVHSC capsids differ from each other by one to four amino acids, resulting in differences in biodistribution and transduction efficiencies. As described in the manuscript, AAVHSC16 has two unique amino acids, 501I and 706C, in addition to 505R that is shared across six AAVHSC serotypes. A series of experiments demonstrated that these amino acids contribute to AAVHSC16s unique properties, which include significantly reduced liver tropism compared to other AAVs, no liver enzyme elevations, and high tissue tropism to the CNS and other peripheral organs. Specifically, these data demonstrated:

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Naturally Occurring Variations in AAVHSC16 Alter Cellular Binding Affinity In Vitro

AAVHSC16 does not share the galactose (a type of glycan) binding feature of other AAVHSCs and Clade F AAVs in vitro. AAVHSC16 did not show improved binding or a difference in number of vector genomes (vgs) or eGFP expression in cells with terminally exposed galactose, while other AAVHSCs tested did.

The combination of the unique naturally occurring amino acids at positions 501I and 505R in AAVHSC16 were shown to contribute to reduced galactose-binding.

AAVHSC16 Has Significantly Reduced Liver Transduction in In Vivo and In Vitro Models, with High Tropism to other Tissues Following a Single I.V. Administration

In murine models, a single I.V. administration of AAVHSC16 showed significantly lower levels of liver tropism compared to AAVHSC15 and AAV9. The liver was the only organ with significant differences as AAVHSC16 demonstrated high levels of tropism to all other organs evaluated, including the brain, heart and muscle; these levels were comparable to those observed with AAVHSC15 and AAV9.

Further, in non-human primates (NHPs), a single I.V. administration of AAVHSC16 resulted in substantially lower liver expression than AAVHSC15, while maintaining high and equivalent levels of transduction in the brain, heart and muscle.

In vitro data also showed that AAVHSC16 led to lower expression in primary human liver cells compared to other tested wild type AAVHSCs and AAV9, and it revealed that AAVHSC16s 706 residue was the main contributor to this outcome.

AAVHSC16 Did Not Lead to Elevations in Liver Function Tests

In NHPs, a single I.V. administration of AAVHSC16 at 7E+13 and 1E+14 vg/kg doses did not result in elevated ALT (alanine transaminase) or AST (aspartate transferase) levels at any timepoint post-dose compared to baseline levels or vehicle-treated controls.

Comparing AAVHSC16 liver transduction and ALT and AST levels to AAV9 and other AAVHSCs further suggested that the lack of ALT and AST elevations with AAVHSC16 is associated with its lower liver tropism.

The publication, Natural Variations in AAVHSC16 Significantly Reduce Liver Tropism and Maintain Broad Distribution to Periphery and CNS, was peer-reviewed and published in the journal Molecular Therapy - Methods & Clinical Development. For more information, please click here or http://www.homologymedicines.com/publications.

About Homology Medicines, Inc.Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. The Companys clinical programs include HMI-102, an investigational gene therapy for adults with phenylketonuria (PKU); HMI-103, a gene editing candidate for PKU; and HMI-203, an investigational gene therapy for Hunter syndrome. Additional programs focus on metachromatic leukodystrophy (MLD), paroxysmal nocturnal hemoglobinuria (PNH) and other diseases. Homologys proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus (AAVHSCs) vectors to precisely and efficiently deliver genetic medicines in vivo through a gene therapy or nuclease-free gene editing modality, as well as to deliver one-time gene therapy to produce antibodies throughout the body through the GTx-mAb platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases. Homology believes its initial clinical data and compelling preclinical data, scientific and product development expertise and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit http://www.homologymedicines.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the potential to expand the application of AAVHSC16 to other disease areas; our expectations surrounding the potential, safety, and efficacy of our product candidates; the potential of our gene therapy and gene editing platforms; and our position as a leader in the development of genetic medicines. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property; risks associated with international operations, such as political and economic instability, including in light of the conflict between Russia and Ukraine; and significant costs incurred as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, and our other filings with the Securities and Exchange Commission (SEC) could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company Contacts:Theresa McNeelyChief Communications Officer and Patient Advocatetmcneely@homologymedicines.com781-301-7277

Media Contact:Cara Mayfield Vice President, Patient Advocacy and Corporate Communications cmayfield@homologymedicines.com 781-691-3510

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Homology Medicines Announces Peer-Reviewed Publication on Novel Discovery of AAVHSC with Robust Distribution to the Central Nervous System and...

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