June 8, 2017 This image shows human heart muscle cells growing in the 3D tissue structure. The cells have been stained with fluorescent molecules to identify the nuclei in blue, and cardiac-specific protein, in green. Credit: Agency for Science, Technology and Research (A*STAR), Singapore

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR have engineered a three-dimensional heart tissue from human stem cells to test the safety and efficacy of new drugs on the heart.

"Cardiotoxicity, which can lead to heart failure and even death, is a major cause of drug withdrawal from the market. Antibiotics, anticancer and antidiabetic medications can have unanticipated side effects for the heart. So it is important to test as early as possible whether a newly developed drug is safe for human use. However, cardiotoxicity is difficult to predict in the early stages of drug development," said Professor Jackie Y. Ying, Executive Director at IBN.

A big part of the problem is the use of animals or animal-derived cells in preclinical cardiotoxicity studies due to the limited availability of human heart muscle cells. Substantial genetic and cardiac differences exist between animals and humans. There have been a large number of cases whereby the tests failed to detect cardiovascular toxicity when moving from animal studies to human clinical trials.

Existing screening methods based on 2-D cardiac structure cannot accurately predict drug toxicity, while the currently available 3-D structures for screening are difficult to fabricate in the quantities needed for commercial application.

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To solve this problem, the IBN research team fabricated their 3-D heart tissue from cellular self-assembly of heart muscle cells grown from human induced pluripotent stem cells. They also developed a fluorescence labelling technology to monitor changes in beating rate using a real-time video recording system. The new heart tissue exhibited more cardiac-specific genes, stronger contraction and higher beating rate compared to cells in a 2-D structure.

"Using the 3-D heart tissue, we were able to correctly predict cardiotoxic effects based on changes in the beating rate, even when these were not detected by conventional tests. The method is simple and suitable for large-scale assessment of drug side effects. It could also be used to design personalized therapy using a patient's own cells," said lead researcher Dr Andrew Wan, who is Team Leader and Principal Research Scientist at IBN.

The researchers have filed a patent on their human heart tissue model, and hope to work with clinicians and pharmaceutical companies to bring this technology to market.

This finding was reported recently in the Biofabrication journal.

Explore further: Stem cell-based screening methods may predict heart-related side effects of drugs

More information: Hong Fang Lu et al. Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening, Biofabrication (2017). DOI: 10.1088/1758-5090/aa6c3a

Coaxing stem cells from patients to become heart cells may help clinicians personalize drug treatments and prevent heart-related toxicity.

Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional 'beating' human heart muscle from stem cells.

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Human heart tissue grown from stem cells improves drug testing - Medical Xpress

Cardiac Stem Cells Comments Off on Human heart tissue grown from stem cells improves drug testing – Medical Xpress | June 8th, 2017

Patients with rare blood cancer brought back to normal - The Hindu The Hindu Undergo bone marrow transplant at Apollo Cancer Institute. and more »

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Xconomy Boston

If youve donated blood, you probably received a follow-up message asking you to consider a platelet donation. Donation centers must constantly replenish their blood supplies, but the need for platelets is particularly acute. Compared to other components of blood, platelets are fragile and short lived, which puts high demand on the small supply of these cell fragments that are key to stopping bleeding.

Plasma separated from blood can be frozen and red blood cells can be refrigerated for up to 42 days. But platelets, which must be stored at room temperature, last just five days. After pathogen screening and transport, platelets have about two days to reach a patient, says Sven Karlsson, president and co-founder of Boston-based Platelet Biogenesis.

Karlssons startup aims to bring hospitals an alternative: platelets produced as needed from stem cells. Platelet BioGenesis, a spinout from Harvard University and Brigham and Womens Hospital, now has $10 million from a Series A round of funding to support preclinical testing of its regenerative medicine technology.

The body produces the components of blood in bone marrow. Platelets are made by a type of bone marrow cell called a megakaryocyte. Platelet Biogenesis produces its platelets in a two-step process. It first develops megakaryocytes from stem cells in culture, Karlsson says. Next, the megakaryocytes are fed into a device that the company developed that puts the cells through a process the company says is similar to what occurs in natural bone marrow physiology and results in the production of platelets.

Were making real, functional platelets, Karlsson says. Instead of mimicking the platelet, were mimicking the process of making a platelet.

Platelet transfusions are needed by patients whose bodies dont produce enough platelets, as well as those who have clotting problems. These transfusions are also used to treat patients who have cancer or are undergoing surgery. Since most platelet donation centers are in urban areas, the short shelf life of platelets makes supplies tight in rural areas. Donations dont entirely solve the problem, Karlsson says. While donating whole blood takes about 15 minutes, platelet donation takes 90 minutes, which makes it harder to get donors.

Researchers have tried to address the platelet shortage problem by developing synthetic platelets. But Karlsson says that the synthetic versions can cause side effects. The idea for replicating the bodys process of producing platelets stems from more than a decade of research. Jonathan Thon, the CEO and co-founder of Platelet BioGenesis, was pursuing ways to extend the shelf life of platelets. But Karlsson says Thon concluded a better approach might be developing a way to replace human donors. As a post-doctoral researcher at Harvard, he invented a microfluidic device that mimics a human bone marrow.

Before Platelet BioGenesis can bring its platelet-making technology to the market, it will need FDA approval. The regulator treats blood products as therapeutics, which means that the company will need to conduct clinical trials. Karlsson says the funding round will support preclinical research. Within three years, he expects the startup will be able to start Phase 1 safety studies. For those trials, Platelet BioGenesis will need to raise additional funds. The current financing round was led by Qiming US Healthcare Fund and included participation from Vivo Capital, VI Ventures, Adena Partners, eCoast Angels, as well as other unidentified investors.

If Platelet BioGenesis wins FDA approval, Karlsson says the company plans to become a manufacturer, selling its platelets in the existing blood supply chain. Its early to talk about pricing, but he says that Platelet Biogenesis products could be more affordable because they are produced from a pathogen-free source. They could also be produced on demand. While the startups platelets should have the same shelf-life as platelets from human donors, Karlsson says that the parent cells that produce platelets can be stored frozen. When platelets are needed, thawed cells can be placed in the companys microfluidic device, which produces platelets within hours.

Karlsson says Platelet BioGenesis might be able offer another advantage: beating the five-day shelf life of donor platelets. In the body, a platelet lasts 10 days. If all of Platelet BioGenesis platelets are born on the same day, they should theoretically have the same 10-day life, he says. Thats one of the things the company plans to test in upcoming trials. The company will also evaluate its platelets to make sure that they are comparable to donor platelets.

Imageby Wikimedia user Erhabor Osarovia a Creative Commons license.

Frank Vinluan is editor of Xconomy Raleigh-Durham, based in Research Triangle Park. You can reach him at fvinluan [at] xconomy.com

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June 8, 2017 One example of STAT1 GOF Mutation phenotype. Credit: Hiroshima University

Researchers report the first-ever study assessing how patients with "gain of function" mutation of the STAT1 gene respond to stem cell transplantation. It involved 15 young patients from nine different countries, each suffering a range of complications caused by the gene's mutation.

Of these, only six survived a regime of stem cell transplantationwith five completely cured and disease free by the study's conclusion.

The study was carried out by Dr. Satoshi Okada (Hiroshima University), Professor Jennifer Leiding (University of Florida), Professor Tomohiro Morio (Tokyo Medical and Dental University), and Professor Troy Torgerson (University of Washington).

Dr. Okada, who first discovered the STAT1 gain of function mutation in 2011, says, "Overall, this result is disappointing but the fact that five patients were cured proves that treatment with stem cells can work, and we now need to learn from these 15 individual cases."

The STAT1 gene plays a vital role in the body's immune system. Rare mutations can lead to STAT1's over-activation (GOF) and autoimmunity.

While the majority of patients afflicted typically show mild to moderate symptoms involving fungal (mostly Candida), bacterial, and viral infectionsabout 10 percent of cases are severe and life threatening.

Until now, developing suitable treatments has been challenging; e.g. anti-fungal drugs temporarily treat the symptoms but not the source mutation, and immunosuppressive therapies often do more harm than good by knocking out already overburdened immune systems.

With only one confirmed case prior to this study of a sufferer being successfully cured using stem cell transplantation, researchers are keen to build an understanding of best practices in order to offer real hope for the typically young sufferers of this condition.

The 15 selected patients were sourced via an international appeal to transplant centers and consortiums. Their ages ranged from 13 months to 33 years at the time of treatment. Screening by HU researchers confirmed that each had the STAT1-GOF mutation, and that the mutation was the source of their ailments.

Treatment was carried out independently by centers around the world. It used chemotherapy to eradicate the host's bone marrowthe source of the damaging STAT1 mutation in these patients. Healthy stem cell cultures sourced from donors were then transplanted into the subjects with the aim of reconstituting their bone marrow to a mutation-free, disease-fighting state.

The researchers suspect three reasons for the low 40 percent success rate:

In response, the researchers have made several proposals for improving this treatment. Due to most of the patients having mild to moderate ailments, only those suffering from severe symptoms should undergo this treatment. In addition, the chemotherapy dosage should be reduced. Those who received low-dose chemotherapy reacted better.

However, a balance must be struck. Low-dose chemotherapy may not eradicate host bone marrow to the extent required for its reconditioning the chance of transplant rejection is thus increased. With this in mind, support treatment may be required to neutralize host antibodies and prevent attacks of introduced stem cells.

Finally, due to the relative success seen in younger patients, stem cell transplantation should occur at as early an age as possible. Due to recent advancements in STAT1-GOF diagnosis, early detection is now a very real possibility hopefully leading to greater success rates, and less suffering for those carrying this potentially devastating mutation.

Explore further: 'Smart' genetic library makes disease diagnosis easier

More information: Jennifer W. Leiding et al. Hematopoietic stem cell transplantation in patients with Gain of Function STAT1 Mutation, Journal of Allergy and Clinical Immunology (2017). DOI: 10.1016/j.jaci.2017.03.049

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This week alone in the news weve seen air strikes, suicide bombings and murders caused by hate. Violence over the hue of someones skin, the way they speak or how they dress. Hate-filled speech by neighbors at meetings and on Facebook. At dinner yesterday, my 8-year-old step-daughter asked her dad, Whats a bomb? My heart is heavy.

Its easy to forget that we are more alike than we are unalike. I offer to you a different perspective.

Six years ago my brother got the call he had Hodgkin Lymphoma, a cancer that starts in cells that are part of the bodys immune system. He was 28 years old. It started as a visible lump under his collar bone, and sometimes you wonder how can so much suffering be caused by such a little lump? And so my story begins.

About one year into his treatment, he reached remission, and from there he was required to undergo an autologous stem cell transplant (a transplant using his own stem cells) to replace his bone marrow and stem cells that were destroyed by chemotherapy and radiation. Fast-forward 10 or so months and my brothers cancer returned. This time the treatment plan had to change his body needed help actually fighting the cancer cells, rather than just a replenishment of normal blood cells. This time around, he required an allogeneic stem cell transplant (a transplant using the stem cells from a healthy donor) and as his sister, I needed to be tested to see if I was a tissue match.

This was all new to me and our family. You hear a lot about cancer. We all know someone who has it, if you dont have cancer yourself. But I knew nothing about stem cell transplants or what it meant to be a donor. First we had to find out if my brother and I were a match.

I received a kit in the mail and all I had to do was swab the inside of my cheek, place the swab inside a sealed bag, and mail it back to the hospital. A week or so later, my brother got the news from his doctor that changed our lives. I was, in fact, a match a near perfect match and we could move forward with his second stem cell transplant.

At this point in my story, youre probably thinking, Of course, youd be a match, youre his sister. I assumed so, as well. Read on.

On Aug. 12, 2016, my brother and I underwent our stem cell transplant at Dana Farber/Brigham and Womens Hospital in Boston. There are two different ways to donate stem cells peripheral blood stem cells (stem cells extracted from your blood after receiving five days of injections of a drug called filgrastim, used to increase the number of blood-forming cells in your bloodstream) and bone marrow (a surgical procedure where doctors use needles to withdraw liquid marrow from both sides of the back of your pelvic bone). Due to my brothers specific treatment plan, he required pure bone marrow, and my bone marrow was taken from my pelvis. Two liters worth of my bone marrow was processed at Dana Farber and then brought to my brother immediately, who received it via an IV drip.

So how does my story end? Why am I telling you all this?

My brother is thriving. My pelvis has healed. And we were absolutely blessed to find a match right within our family.

The reality is that fewer than 30 percent of patients with a blood cancer or blood disease will find a related-donor; the other 70 percent, thousands of patients with blood cancers like leukemia and lymphoma, sickle cell anemia or other life-threatening diseases, depend on the national bone marrow registry to find a match to save their life. Some day you or someone you love might depend on a complete stranger who might be a Muslim, a Republican, gay or straight. But it wont matter because from the inside, they will be the same.

I plead with you to remember that we are more alike than we are unalike, and to do something positive for humanity.

You can visit http://www.bethematch.org and join the Be The Match national bone marrow registry.

Or you can attend one of my in-person donor drives in Greenfield over the next few months. The first will be this Saturday, June 10, from 2 to 4 p.m. at the Pints in the Park event at the Greenfield Energy Park.

If you are between the ages of 18 and 44, patients especially need you. You could be someones cure.

I note the obvious differences

between each sort and type,

but we are more alike, my friends,

than we are unalike.

We are more alike, my friends,

than we are unalike.

From Human Family, a poem by Maya Angelou

Ashli Stempel is a Greenfield resident and a member of the Greenfield Town Council.

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My Turn: Do something within your power to save another life - The Recorder

Bone Marrow Stem Cells Comments Off on My Turn: Do something within your power to save another life – The Recorder | June 8th, 2017

Whats trending in cosmeceuticals? Niacinamide, heparan sulfate, defensins, novel retinoids and sodium copper chlorophyllin complex, according to Vivian W. Bucay, M.D., a dermatologist in San Antonio, Texas, who presented on the topic this week at the 2017 Vegas Cosmetic Surgery and Aesthetic Dermatology meeting, in Las Vegas.

Niacinamide

Cosmeceuticals contain three primary forms of vitamin B3, including niacinamide, nicotinic acid and nicotinate esters, according to Dr. Bucay.

[The] most studied and efficacious form is niacinamide. Nicotinic acid [is] not generally used because it causes vasodilation, redness and irritation, according to Dr. Bucays presentation. Niacinamide readily penetrates the stratum corneum, [with] little potential for irritation.

Niacinamides effects on the skin include improving the skin barrier function, pigmentation and appearance of lines and wrinkles associated with photoaging. The water-soluble vitamin has been shown in studies to have immunomodulatory and anti-inflammatory effects, and more. Niacinamide has also been shown to improve acne, by, among other things, decreasing facial sebum production. It also has been shown to reduce pigmentation and decrease UV-induced immunosuppression.

Heparan Sulfate

Heparan sulfate is a key glycosaminoglycan, which surrounds cells and is required for cell growth, according to Dr. Bucay.

Heparan sulfate is well documented in dermatology, with studies in wound repair, skin infections, atopic dermatitis, rosacea and psoriasis. As a facilitator of growth factor function, heparan sulfate is essential for collagen synthesis, she writes.

And topically applied heparan sulfate penetrates the epidermis and dermis in humans, according to Dr. Bucay.

Low molecular weight heparan sulfate is found exclusively in the Sent skincare product line (Sent), she writes.

Defensins

According to a study by Lough et al published November 2013, the immune system releases defensins that activate LGR6+ stem cells. Activated LGR6+ stem cells create new basal stem cells. And the newly-created basal stem cells produce fresh keratinocytes that last a lifetime.

Defensins, which are antimicrobial peptides, are released by neutrophils in wounds. These dermatologic stem cells generate cell lineages of the skin, according to Dr. Bucay.

Defensins have been shown to enhance wound healing and hair growth. Early studies suggest defensins reduce skin aging. Dr. Bucay is among the researchers conducting an ongoing vehicle-controlled study on the use of synthetic defensins in a cosmetic base.

While retinol stimulates old basal stem cells to make old keratinocytes, defensins activate preserved LGR6+ stem cells to make new basal stem cells. And while growth factors switch on good and bad cells, defensins activate specific cells types to do specific jobs, according to Dr. Bucay.

Defensins are found in DefenAge (DefenAge) skincare products.

A novel retinoid

Scientists have developed a bioengineered double conjugate retinoid with lactic acid, which is designed to optimize delivery of beneficial properties of both an alpha hydroxy acid (AHA) and a retinoid, with less skin irritation. The proprietary AlphaRet technology increases stability, reduces irritation and improves passage through the skin, according to Dr. Bucays presentation.

The product AlphaRet Overnight Cream (SkinBetter Science), includes the AlphaRet molecule, 0.1%, glycolic acid and a potent antioxidant blend.

Sodium copper chlorophyllin complex

Liposomal sodium copper chlorophyllin complex technology is based on chlorophyll, [a] fat soluble green pigment in plants necessary for photosynthesis, according to Dr. Bucay.

Sodium copper chlorophyllin has a long history of use in medicine, including in topical wound healing. Recently, sodium chlorophyllin has been used topically for cosmetic purposes, in the MDRejuvena Rejuvaphyl Rejuvenating complex (MDRejuvena). The product, she writes, has been shown to reduce redness and oiliness and improve signs of photodamage.

Results from a human biopsy study published July 2016 suggest retinoids and sodium copper chlorophyllin complex have beneficial effects on biomarkers of photoaged skin. Together, sodium copper chlorophyllin complex and retinols may provide a dual approach to reversing age-related changes, according to the authors.

Disclosure: Dr. Bucay reports ties to Allergan, Merz Aesthetics, Galderma, Johnson & Johnson/Neutrogena, LOreal/SkinCeuticals, NuGene, Sent Labs, Medicell Technologies, Alastin Skincare, Viviscal, BTL, Sienna Biopharmaceuticals, Syneron Candela and Miramar Labs.

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Skin Stem Cells Comments Off on Trends in cosmeceutical ingredients – ModernMedicine | June 8th, 2017

Shares of Shire (SHPG) were down $3.22 or 1.85% in early trading Wednesday to $170.88 after the company said it would transfer its U.S. investigational new drug application for for Graft-Versus-Host Disease candidate Alpha-1 Antitrypsin to Kamada (KMDA) . The treatment is aimed at addressing complications fromstem cell or bone marrow transplants.

Kamada is developing the drug in Europe. Kamada shares were down nearly 7% to $7.64.

Calithera Biosciences (CALA) was up to $16.10, a spike of 70 cents or 4.55%, after the FDA designated the company's lead product candidate, CB-839, in combination with Novartis' AFINITOR for Fast Track review for the treatment of metastatic renal cell carcinoma in patients who have received at least two prior lines of therapy.

Shares of Synergy Pharmaceutical (SGYP) rose 4.5% to $4.15 after the FDA accepted for review its supplemental New Drug Application for TRULANCE a candidate to treat irritable bowel syndrome with constipation. The FDA approved TRULANCE to treat chronic idiopathic constipation in January.

Over at Real Money, Bret Jensen looks at 4 Undervalued Biotech Stocks.

Also, Jim Cramer and the AAP team offer up stocks that will allow you to play it safe amid crazy politics.

In terms of volume, Johnson & Johnson (JNJ) and Sanofi (SNY) were among the most actively traded stocks midmorning but were both only down less than a percent.

Exact Sciences (EXAS) was trading at twice its daily volume and saw its shares fall about 6.6%, or $2.40, in early trading Wednesday to $34.19 apiece.

The Madison, Wisc.-basedmolecular diagnostics company said after markets closed on Tuesday that its underwriters, includingJefferies LLC, BofA Merrill Lynch and Robert W. Baird & Co. hadacuired7 million shares of commons stock with an option to buy about 1 million more.

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Biotech Movers: Shire Falls on Stem Cell Program Transfer; Calithera, Synergy Up on FDA Approvals - TheStreet.com

Bone Marrow Stem Cells Comments Off on Biotech Movers: Shire Falls on Stem Cell Program Transfer; Calithera, Synergy Up on FDA Approvals – TheStreet.com | June 7th, 2017

June 6, 2017 Drs. Carlos Isales, Meghan McGee-Lawrence, William D. Hill and Mark Hamrick. Credit: Phil Jones

With age, the form and function of our bones and muscles drop off, putting us as increased risk for frailty and falls.

Now researchers at the Medical College of Georgia at Augusta University are dissecting just what happens to the stem cells that make the tissues, which help keep us upright, with an eye on improving our healthspan.

Osteoporosis already is a major public health problem affecting about 44 million Americans and costing billions annually. The world's older population is growing at an unprecedented rate with 8.5 percent of the worldwide population - 617 million people - age 65 and older, a proportion estimated to reach 17 percent by 2050, according to the National Institute on Aging.

"After age 65 you start losing about 1 percent of both muscle and bone per year," said Dr. Carlos Isales, endocrinologist, Regents' professor and vice chair for clinical affairs in the MCG Department of Neuroscience and Regenerative Medicine.

"Daily exercise decreases the slope of that decline. But what we are focusing on is trying to see if we can flatten the curve even further," said Isales, principal investigator on a new $9.3 million Program Project grant from the National Institutes of Health.

Time seems to alter the dynamic between the mesenchymal stem cells making bone and muscle and the amino acids that fuel them. The MCG scientists also have evidence it changes the signals stem cells send each other.

The bottom line: Our stem cell population gets reduced and the cells we have become less efficient at making bone and muscle, often opting for the easier task of making fat instead, Isales said.

The team, which includes principal investigators bone biologist Dr. Mark Hamrick, stem cell researcher Dr. William D. Hill and biomedical engineer Dr. Meghan McGee-Lawrence, wants to keep stem cells focused on making bone and muscle.

"We are looking at stem cells as a group and what is happening to them as we age," Hill noted. "This includes a loss of direction so they aren't as functional as they were before. The other thing we are looking at is their survival and their numbers."

"We are trying to figure out why the changes are happening and if we can target those cells to make them want to make bone again," McGee-Lawrence said.

Much as the function of bone and muscle is interwoven, so is their health and the factors that promote their loss or survival also are similar, said Hamrick.

A major culprit in their breakdown appears to be the metabolite kynurenine, a byproduct of the essential amino acid tryptophan. Tryptophan is among the nine amino acids our body can't make and we must consume in foods like turkey and soybeans so we can perform essentials like making protein. The researchers also think the fuel sends signals to cells, ones that aging stem cells apparently don't get.

The unhealthy metabolite is the result of a natural action called oxidation, which occurs anytime cells use oxygen. Particularly with age, the free radicals produced by oxidation can also damage cells. Kynurenine results when the enzyme, indoleamine 2,3 dioxygenase, or IDO, which a variety of tissues make to help moderate an immune response, oxidizes tryptophan. Over time, kynurenine piles up and appears to alter the dynamic of bone and muscle formation.

Again, somewhat ironically, the many functions of essential amino acids include working as antioxidants, so the researchers are putting together nutrient cocktails - minus tryptophan and with reduced protein content - that they hope can reverse age-related damage. Isales notes that they may find that other amino acids produce similar problems as tryptophan in the aged environment.

So they also are taking more direct approaches like whether an IDO inhibitor - which is already in clinical trials as a cancer fighter - can reverse changes and get stem cells to regain more youthful function.

In an effort to begin to see if what they have seen in laboratory mice holds up in humans, they are trying both approaches in human stem cells retrieved during the process of a knee or hip replacement by colleagues in the MCG Department of Orthopaedic Surgery.

They have laboratory evidence that in mice at least, high kynurenine levels impact the ability of cells in the bone marrow to make bone-forming cells called osteoblasts. In fact, even relatively young mice fed kynurenine experience bone loss, an increase in bone destruction by cells called osteoclasts and increased fat in their bone marrow. Conversely, mice with IDO knocked out maintain strong bone mass.

"You can make an old mouse young and you can make a young mouse old," Hill noted.

The team also has evidence that part of how age-related increases in kynurenine does damage is by altering microRNAs - small but powerful pieces of RNA that can control expression of hundreds of genes at the same time - as well as vesicles called exosomes that are hauling the microRNAs around. Stem cells secrete exosomes as one way to communicate, and apparently aging stem cells don't communicate well with each other.

"Exosomes are one mechanism of crosstalk between cells and also between different organs," said Hamrick. "Your liver is producing exosomes, fat produces exosomes, they will hit other organs and they carry, in some cases, positive messages and in some cases bad messages," said Hamrick, who is leading this project to restore positive messaging.

They have laboratory evidence that aging alters at least two microRNAs, miR-141 and miR-183, which prompts cells to make bone-eating instead of bone-forming cells. Again, they have shown that even young stem cells exposed to older exosomes will assume this bone-reducing stance. But they also have some evidence that some of the dietary interventions Isales is looking at could reverse the ill effects.

The team recently reported in the journal Tissue Engineering that exosomes from old and younger mice were similar in size and number and both had a lot of miRNAs. But aged exosomes had significantly and specifically more mi183, an miRNA already associated with cancer. In this case, high mi183 appears to decrease cell proliferation and the ability of immature cells to become bone cells and to support the general deterioration that comes with age, called senescence. Age-related increases of reactive oxygen species and oxidative stress help increase mi183 levels and these undesirable results. When researchers treat mesenchymal stem cells from young animals with exosomes from old mice, is suppresses formation of muscle-making genes; giving mi183 directly to bone and muscle producing cells makes them start acting old. Now they want to know more about how aging changes the secretion and cargo of exosomes by mesynchymal stem cells and how that in turn contributes to bone and muscle loss.

A third project, led by Hill, will focus on the cargo, the miRNAs, to learn more about exactly how they impact bone formation and turnover. "We think that the amino acids are controlling the expression of specific sets of microRNA," Hill said. That means they may want to target and even eliminate key or critical microRNAs, which could obviously affect expression of numerous genes as a result.

They also are exploring aging's impact on stromal cell derived factor 1, or SDF-1, which is critical to helping keep stem cells in the bone marrow and focused on making bone. Age-related changes appear to make SDF-1 instead encourage stem cells to wander. The researchers note that while these cells do often need to leave the bone marrow, to say help heal an injury, these age-related travels are random and often cells don't find their way back. A consistent goal is identifying intervention targets.

"The idea is if we can change the environment and change how they are signaling to themselves and to other cells, we can modify the stem cell directly that way," Hill said.

They are looking upstream as well for earlier points of intervention, including what is happening to histone deacetylase-3, or HDAC3. They have evidence that HDAC3, another pervasive regulator in the body that can turn gene expression up or down, is important in stem cells' age-related propensity to make fat instead of bone.

At least one reason is that reduced HDAC3 means less bone, which literally makes more room for fat, said McGee-Lawrence, who is leading these studies. Her previous studies have shown that when HDAC3 is deleted from the skeleton, bones are weaker, much like what occurs with aging.

Now they have evidence that mice treated with kynurenine, for example, have suppressed HDAC3 expression in the bone. They want to know more about just how HDAC3 gets suppressed as we age and exactly what that does to bone formation and fat storage besides just making room. The new grant is allowing them to put the pieces together better, looking further at just what suppresses HDAC3 and what suppression does to bone versus fat formation. The bottom line again is identifying early points of intervention and potentially nutrients to intervene.

"Something in the microenvironment of the bone is causing the cells, instead of wanting to make bone, they are storing a lot of fat," McGee-Lawrence said. "Some of these epigenetic factors, like HDAC3, some of the environmental factors like changes in the amino acids are causing the cells to dysfunction. We are hoping to figure out what that signal is and how to reverse it and to make those cells want to start making bone again."

Identical twin studies have shown that environmental factors definitely play a role, since the bone/muscle health of these twins often is not identical even though their genes are, Isales said. Rather than changing the genes themselves, environmental factors appear to have changed their expression: which ones are turned or on off. These epigenetic changes include factors from diet to stress to sleep patterns to age.

There are 20 amino acids, which are essential to protein production and a variety of other functions from giving cells structure to helping organs functions. Kyrurenine also is associated with the degeneration of our brain and immune system as we age. Mesynchymal stem cells also produce blood, cartilage and fat cells.

Isales also is vice chair of clinical and translational research in the MCG Department of Orthopaedics and a faculty member in the MCG Department of Medicine. Hamrick, Hill and McGee-Lawrence are all faculty members in the MCG Department of Cellular Biology and Anatomy. Other scientists helping support three core laboratories for the interrelated studies include the Administrative Core with Biostatistics, Maribeth Johnson and Dr. Jie Chen, MCG Department of Biostatics and Epidemiology; the Bone Biology Core, Dr. Mohammed Elsalanty, Department of Oral Biology, Dental College of Georgia at AU; and the Bone Stem Cell Core, Dr. Xingming Shi, MCG Department of Neuroscience and Regenerative Medicine.

Explore further: Non-coding RNA molecule could play a role in osteoporosis

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Major research initiative explores how our bones and muscles age, new ways to block their decline - Medical Xpress

Bone Marrow Stem Cells Comments Off on Major research initiative explores how our bones and muscles age, new ways to block their decline – Medical Xpress | June 7th, 2017

June 6, 2017 ISkin (three-dimensional cultured skin) derived from human iPSCs. Immunohistochemical analysis with antibodies to KERATIN 14 (KRT14), p63, cytokeratins (Pan-CK), involucrin, laminin 5, loricrin, KRT10, and filaggrin. The multilayered epidermis expressed KRT14, involucrin, laminin 5, Pan-CK, loricrin, KRT10, and filaggrin in iSkin, indicating that iPSC-keratinocytes terminally differentiate in the skin equivalents. Scale bar is 100 m. Credit: Kazuhiro Kajiwara.

Myelomeningocele is a severe congenital defect in which the backbone and spinal canal do not close before birth, putting those affected at risk of lifelong neurological problems. In a preclinical study published June 6th in Stem Cell Reports, researchers developed a stem cell-based therapy for generating skin grafts to cover myelomeningocele defects before birth. They first generated artificial skin from human induced pluripotent stem cells (iPSCs), and then successfully transplanted the skin grafts into rat fetuses with myelomeningocele.

"We provide preclinical proof of concept for a fetal therapy that could improve outcomes and prevent lifelong complications associated with myelomeningoceleone of the most severe birth defects," says senior study author Akihiro Umezawa of Japan's National Research Institute for Child Health and Development. "Since our fetal cell treatment is minimally invasive, it has the potential to become a much-needed novel treatment for myelomeningocele."

Myelomeningocele, which is the most serious and common form of spina bifida, is a neural tube defect in which the bones of the spine do not completely form. As a result, parts of the spinal cord and nerves come through the open part of the spine. A baby born with this disorder typically has an open area or a fluid-filled sac on the mid to lower back. Most children with this condition are at risk of brain damage because too much fluid builds up in their brains. They also often experience symptoms such as loss of bladder or bowel control, loss of feeling in the legs or feet, and paralysis of the legs.

Babies born with myelomeningocele usually undergo surgery to repair the defect within the first few days of life. Some highly specialized centers also offer intrauterine surgery to close the defect before the baby is born. Although prenatal surgery can improve later neurological outcomes compared with postnatal surgery, it is also associated with higher rates of preterm birth and other serious complications, underscoring the need for safe and effective fetal therapies.

To address this problem, Umezawa and his team set out to develop a minimally invasive approach for generating and transplanting skin grafts that could cover large myelomeningocele defects earlier during pregnancy, potentially improving long-term outcomes while reducing surgical risks. In particular, they were interested in using iPSC technology, which involves genetically reprogramming patients' cells to an embryonic stem cell-like state and then converting these immature cells into specialized cell types found in different parts of the body. This approach avoids ethical concerns while offering the advantages of a potentially unlimited source of various cell types for transplantation, as well as minimal risk of graft rejection by the immune system.

In the new study, the researchers first generated human iPSCs from fetal cells taken from amniotic fluid from two pregnancies with severe fetal disease (Down syndrome and twin-twin3 transfusion syndrome). They then used a chemical cocktail in a novel protocol to turn the iPSCs into skin cells and treated these cells with additional compounds such as epidermal growth factor to promote their growth into multi-layered skin. In total, it took approximately 14 weeks from amniotic fluid preparation to 3D skin generation, which would allow for transplantation to be performed in humans during the therapeutic window of 28-29 weeks of gestation.

Next, the researchers transplanted the 3D skin grafts into 20 rat fetuses through a small incision in the uterine wall. The artificial skin partially covered the myelomeningocele defects in eight of the newborn rats and completely covered the defects in four of the newborn rats, protecting the spinal cord from direct exposure to harmful chemicals in the external environment. Moreover, the engrafted 3D skin regenerated with the growth of the fetus and accelerated skin coverage throughout the pregnancy period. Notably, the transplanted skin cells did not lead to tumor formation, but the treatment significantly decreased birth weight and body length.

"We are encouraged by our results and believe that our fetal stem cell therapy has great potential to become a novel treatment for myelomeningocele," Umezawa says. "However, additional studies in larger animals are needed to demonstrate that our fetal stem cell therapy safely promotes long-term skin regeneration and neurological improvement."

Explore further: Prenatal stem cell treatment improves mobility issues caused by spina bifida

More information: Stem Cell Reports, Kajiwara et al.: "Fetal therapy model of myelomeningocele with three-dimensional skin using amniotic fluid cell-derived induced pluripotent stem cells" http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30220-5 , DOI: 10.1016/j.stemcr.2017.05.013

Journal reference: Stem Cell Reports

Provided by: Cell Press

Some bodily activities, sleeping, for instance, mostly occur once every 24 hours; they follow a circadian rhythm. Other bodily functions, such as body temperature, cognitive performance and blood pressure, present an additional ...

Myelomeningocele is a severe congenital defect in which the backbone and spinal canal do not close before birth, putting those affected at risk of lifelong neurological problems. In a preclinical study published June 6th ...

Exactly when does old age begin? Which health markers best predict who will live a long and healthy life versus a life spent in poor health?

A vaccine developed at The Scripps Research Institute (TSRI) to block the "high" of heroin has proven effective in non-human primates. This is the first vaccine against an opioid to pass this stage of preclinical testing.

Yale scientists produced increased grooming behavior in mice that may model tics in Tourette syndrome and discovered these behaviors vanish when histaminea neurotransmitter most commonly associated with allergiesis ...

Delivering drugs to the brain is no easy task. The blood-brain barrier -a protective sheath of tissue that shields the brain from harmful chemicals and invaders - cannot be penetrated by most therapeutics that are injected ...

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3-D skin made of stem cells treats backbone birth defect in rodents - Medical Xpress

Skin Stem Cells Comments Off on 3-D skin made of stem cells treats backbone birth defect in rodents – Medical Xpress | June 7th, 2017

An experimental therapy to repair spinal cord injury with stem cell-derived tissue is progressing smoothly, according to a leader of that trial who spoke at a conference on stem cell therapy.

The Phase 1 safety trial is proceeding with no complications, said Dr. Joseph Ciacci, a University of California San Diego neurosurgeon. The trial is being conducted at the universitys Sanford Stem Cell Clinical Center. The conference was held last week at the Sanford Consortium for Regenerative Medicine in La Jolla.

With safety looking good, the green light has been given to treat more patients, Ciacci said. However, to produce effectiveness, more cells will need to be transplanted.

Four patients have been treated with neural stem cells, injected into the spinal cord. They had experienced complete loss of motor and sensor function below the injury. They had been injured between 1 and 2 years previously.

Moreover, the cells show signs of integrating with the surrounding tissue in animal studies, Ciacci said. If the preliminary evidence holds up, Ciacci and colleagues plan to submit a paper detailing the results.

Curing paralysis from spinal cord injury was a big selling point for those who successfully advocated Proposition 71, which authorized selling $6 billion in state bonds to establish and fund the California Institute for Regenerative Medicine, or CIRM. The institute got $3 billion, the remaining half is going for interest over the life of the bonds.

While CIRM has been under pressure to show results, doctors are taking great care to establish safety first in the spinal cord treatment, because of potential risks in the procedure.

We are now enrolling and recruiting for the second cohort, which is for chronic cervical spinal cord injuries, Ciacci said. They are medically classified as C5-C7 ASIA A Complete.

Chronic injuries need to have taken place more than 1 year before treatment. For this study, the injury must also be under two years old. The trial is being conducted at UCSD with Ciacci serving as the principal investigator.

For more information on the Phase I Chronic SCI study, contact Ciaccis research group at (619) 471-3698, nksidhu@ucsd.edu.

In addition, the researchers have been approved to start another spinal cord injury trial with a different set of cells. These oligodendrocyte progenitor cells, derived from embryonic stem cells, can turn into several different types of neural cells.

The trial, sponsored by Asterias, treats newly injured patients, between 14 and 30 days after injury.

For more information on the Asterias trial, contact the UCSD Alpha Stem Cell Clinic at 858-534-5932 alphastemcellclinic@ucsd.edu or visit http://www.scistar-study.com and j.mp/ucsdast.

Asterias acquired the technology from Geron, which had undertaken the work with a CIRM grant. Geron later canceled the work and refunded the money to CIRM. Asterias got funding from CIRM to continue the work.

The Asterias trial will use the same technique as used with the Chronic SCI trial, a technique which can improve safety, Ciacci said. The cells will be injected in a series of progressively larger amounts that may give evidence of the dose relates to effectiveness, although safety remains the main concern.

This cell line is cryopreserved, its sent to us as a single dose the day of surgery, Ciacci said. Were going to study different doses 2 million, 10 million, 20 million cells per injection. Its going to be a direct injection, just like what weve done before.

As in previous treatments, patients will also receive immune suppression to prevent rejection of the cells. Likewise, they will be monitored for many years after treatment.

Another trial coming to UCSD will test for efficacy in ALS, Ciacci said.

Ciacci said hes looking for qualified patients for these trials, and urged those in the audience to help find them.

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bradley.fikes@sduniontribune.com

(619) 293-1020

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Stem cell-based spinal cord therapy expanded to more patients - The San Diego Union-Tribune

Spinal Cord Stem Cells Comments Off on Stem cell-based spinal cord therapy expanded to more patients – The San Diego Union-Tribune | June 6th, 2017

The Sun

Bioquark aims to bring brain-dead people back to life next year - Metro Metro It sounds like the plot of a horror movie - but a new trial aims to regenerate the brains of brain-dead people, by injecting them with stem cells. A U.S.... Controversial Study Wants To Resurrect Brain-Dead People ...IFLScience US Firm Tries 'Reawakening The Dead' With Stem Cells [VIDEO]The Daily Caller Company working on a way to reverse deathNEWS10 ABC The Sun -Daily Mail -Stck Nws US all 11 news articles »

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Bioquark aims to bring brain-dead people back to life next year - Metro - Metro

Spinal Cord Stem Cells Comments Off on Bioquark aims to bring brain-dead people back to life next year – Metro – Metro | June 6th, 2017

Activating stem cells Wnt signaling pathways can drive cardiac progenitor cells to become epicardium instead of myocardium cells.

A process using human stem cells can generate epicardium cells that cover the external surface of a human heart, according to a multidisciplinary team of researchers.

In 2012, we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit the Wnt signaling pathway, they become myocardium muscle cells, says Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Pennsylvania State University (Penn State). Myocardium, the middle of the hearts three layers, is the thick, muscular part that contracts to drive blood through the body. The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell using cell-surface receptors.

We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didnt know what that information was, Lian says. Now, we know that if we activate the cells Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells.

Lance Lian/Penn State

The groups results bring researchers one step closer to regenerating an entire heart wall. Through morphological assessment and functional assay, the researchers found that the generated epicardium cells were similar to epicardium cells in living humans and those grown in the laboratory.

The last piece is turning cardiac progenitor cells to endocardium cells (the hearts inner layer), and we are making progress on that, Lian says.

The groups method of generating epicardium cells could be useful in clinical applications, for patients who suffer a heart attack.

Heart attacks occur due to blockage of blood vessels, Lian says. This blockage stops nutrients and oxygen from reaching the heart muscle, and muscle cells die. These muscle cells cannot regenerate themselves, so there is permanent damage, which can cause additional problems. These epicardium cells could be transplanted to the patient and potentially repair the damaged region.

In addition to generating the epicardium cells, researchers can keep them proliferating in the lab after treating them with a cell-signaling pathway Transforming Growth Factor Beta (TGF) inhibitor.

After 50 days, our cells did not show any signs of decreased proliferation. However, the proliferation of the control cells without the TGF Beta inhibitor started to plateau after the tenth day, Lian says.

Pennsylvania State University http://www.psu.edu

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Stem cells regenerate external layer of a human heart - Today's Medical Developments

Cardiac Stem Cells Comments Off on Stem cells regenerate external layer of a human heart – Today’s Medical Developments | June 6th, 2017

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch occured on Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

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SpaceX launches CU-built heart, bone health experiments to space station - CU Boulder Today

Cardiac Stem Cells Comments Off on SpaceX launches CU-built heart, bone health experiments to space station – CU Boulder Today | June 6th, 2017

Photonics.com Jun 2017 MINNEAPOLIS, June 6, 2017 A new 3D-laser-printed patch has been developed that can help heal scarred heart tissue after a heart attack.

Researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

"This is a significant step forward in treating the No. 1 cause of death in the U.S.," said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. "We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years."

The patch is modeled after a digital 3D scan of the structural proteins of native heart tissue. It is then made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.

"We were quite surprised by how well it worked, given the complexity of the heart," Ogle said. "We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch."

The researchers will soon begin working on a larger patch and testing it on a pig heart, which is similar to a human heart.

The research study is published in the American Heart Association journal Circulation Research (doi: 10.1161/CIRCRESAHA.116.310277).

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3D-Printed Patch Mends Hearts - Photonics.com

Cardiac Stem Cells Comments Off on 3D-Printed Patch Mends Hearts – Photonics.com | June 6th, 2017

TAMPA Researchers at the University of South Florida show in a new study that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with the disease amyotrophic lateral sclerosis (ALS) by repairing damage to the blood-spinal cord barrier.

In a study recently published in the journal Scientific Reports, researchers in USFs Center of Excellence for Aging and Brain Repair say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS.

USF Health Professor Svitlana Garbuzova-Davis, PhD, led the project.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.

The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported.

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Mice with ALS improve with stem cell therapy - The Ledger

Bone Marrow Stem Cells Comments Off on Mice with ALS improve with stem cell therapy – The Ledger | June 6th, 2017

Vancouver surgeon and UBC professorRonald Lett is appealing tothe public forhelp in finding a bone marrow transplant for his wife Elizabeth Nega, who has an aggressive form of leukemia.

Nega, better known as Elsa, discovered that she had acute lymphoblasticleukemia in February and urgently needs a bone marrow transplant.However, the Ethiopian Canadian wife and mother of two has been unable to find a match because of the low number of African donors.

Ronald and Elsa are now reaching out to people of African descent to register as bone marrowdonors. They've started a website, match4elsa.com, as well as Facebook and Twitter accounts, to find Elsa and other African-Canadians life saving transplants.

"I love to live. I want to be with my kids. I want to smile again. I want to play with them again. If you save my life, you will save my whole family," said Elsa Nega in her video appeal for a donor.

Lett is the founder and international director of the charity, Canadian Network for International Surgery(CNIS). He met Elsa in Ethiopia while he was there training local doctors to perform essential surgeries.

After dedicating his life to helping others, Lett says being unable to help his wife in her time of need has been difficult.

"I helplessly watch as the love of my life suffers terribly, has devastating complications from her treatmentbut has no promise of a cure," said Lett.

"Transplant, which only works half the time, is our only hopeand all the news concerning a match for Elsahas been bad too."

Elizabeth Nega, Ronald Lett and their two children are running out of time to find Elsa a bone marrow donor. (Helen Goddard)

Since discovering that she had leukemia, Elsahas beenput through several rounds of chemotherapy, but after failing to go into remission, obtaining stem cells from a bone marrow transplant has become her only hope of recovery.

Her brother and sister in Ethiopia were her best chance, but neither were a match.

The larger issue in finding a donor for Elsa is the lack of diversity in the donor registry.

Of the 405,000 Canadians on the stem cell registry, only 800 have an African background, and none are a match for Elsa, according toChrisvan Doornwith the One Match Program.

Even among the 29 million people on the international registry, no match has been found.

Lett and Elsa's children, Lana, 8, and Lawrence, 6, have contributed to the effort.

They're in a video reading a letter appealing to Ethiopians around the world, including Canadian-Ethiopian R & B singerThe Weeknd, asking for help to save their mom.

In the meantime, Elsa's health is declining, and she's hoping for a miracle, even if it's not for her.

"If they save somebody, that's like a lotteryor a big blessing, you know.It's a big chance to get somebody to match to you and save your life.You know many people can't do this." saidNega.

People interested in registering to be a bone marrow donor can register at blood.ca,must be between 17 and 35 years old and in good health.

The test involves a cheek swab at the nearest clinicor a kit can be mailed out.

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Vancouver woman's family pleading for help finding a bone marrow donor - CBC.ca

Bone Marrow Stem Cells Comments Off on Vancouver woman’s family pleading for help finding a bone marrow donor – CBC.ca | June 6th, 2017

Dr Bishesh Poudyal of the Civil Service Hospital in Kathmandu is the doctor who carried out all 18 transplants. At Civil the cost per transplant is between Rs 400,000 to Rs 500,000. KATHMANDU, June 7:A total of 18 bone marrow transplants have been successfully carried out in Nepal by a single doctor in Kathmandu since 2012.

A bone marrow transplant is a medical procedure performed to replace bone marrow that has been damaged or destroyed by disease, viral infection, or chemotherapy. This procedure involves transplanting blood stem cells, which travel to the bone marrow where they produce new blood cells and promote growth of new marrow.

Bone marrow is the spongy, fatty tissue inside the bones. It creates the red blood cells that carry oxygen and nutrients throughout the body, white blood cells that fight infection, and platelets that are responsible for the formation of clots.

Dr Bishesh Poudyal of the Civil Service Hospital in Kathmandu is the doctor who carried out all 18 transplants. "I am going to carry out bone marrow transplants on another six patients in near future," said Poudyal, who was born at Jawalakhel of Lalitpur.

Dr Poudyal, who passed SLC 24 years ago from Adarsha Vidya Mandir, was inspired by his father to pursue studies in hematology and bone marrow transplant. After completing his MBBS from China and MD from India under government scholarships, he started working at the Bir Hospital. "I served there for two years at Bir Hospital as per the government rule for scholarship students," he said.

Then, Dr Poudyal left the Bir Hospital as he came to know that bone marrow transplant was not possible at Bir and joined Civil Service Hospital. He also practised at the Nobel Medical College Hospital at Sinamangal where he started bone marrow transplant in 2012. "As I came to know Nobel was charging patients between Rs 800,000 to Rs 1 million per transplant, I quit the hospital," he said.

At his initiation, the Civil Hospital started bone marrow transplant about a year ago. At Civil the cost per transplant is between Rs 400,000 to Rs 500,000. The transplant recepients ranged from 22 years old to 64 years. Two patients died after about nine months of transplant. "One died of tuberculosis infection and another died of disease complications," according to Dr Poudyal.

"Bone marrow is transplanted in cancer and other blood diseases. Bone marrow is transplanted in different ways-- by treating patients' bone marrow, using siblings' and parents' bone marrow and matched unrelated donor (MUD). "We have not transplanted bone marrow under MUD category," said Dr Poudyal. "MUD is a condition of matching gene with other persons. A person's genes match those of only one percent of the population of the entire world," he added.

There is no actual data of patients with bone marrow problems in the country. However, 400 to 600 patients visit Civil Service Hospital for treatment of acute lukemia and other blood cancer cases per year. "Forty to 50 percent patients of blood cancer recover fully while the recovery rate among bone marrow recepients is 70-80 percent," said Dr Poudyal.

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Nepal's sole bone marrow transplant doctor - Republica

Bone Marrow Stem Cells Comments Off on Nepal’s sole bone marrow transplant doctor – Republica | June 6th, 2017

Paul Spagnuolo is working on creating a drug with an avocado compound that targets cancer cells. (Paul Spagnuolo)

A Guelph food science researcher is getting $100,000 from the Ontario Institute for Cancer Research to fund investigations into using an avocado compound as a possible treatment for leukemia.

Paul Spagnuolo discovered that Avocatin B, a compound mainly found in avocado pits can kill leukemia stem cells in 2015.

"Getting funds to do any type of research is a reason to celebrate," said Spagnuolo told CBC News.

The funding will further his research by allowing his lab to use better equipment and collaborate with cancer researchers from the University of Toronto, Princess Margaret Cancer Centre, Ottawa University and McMaster University.

Spagnuolo's lab tested more than 800 natural compounds for their ability to kill leukemia stem cells and discovered Avocatin B was the most potent and only targetedcancer cells.

Avocatin B kills leukemia stem cells by stopping fatty acid oxidation in the cells, a process necessary for the cancer cell to digest fat as a fuel source in order to live and grow.

"Our cells can utilize glucose primarily and some other parts, but leukemia cells are rewired so that if you inhibit the oxidation process, they will die," he said.

Spagnulo and his lab are now looking to develop a way to detect whether or not Avocatin B is circulating in the blood and bone marrow.

Leukemia cells live in the bloodstream or bone marrow, so it's important for the drug to make it to those parts to kill the cancer cells.

"We want to be able to detect our drug inside the blood so that we can understand how we can formulate products better to get our product into the blood," said Spagnuolo.

Moving forward, Spagnuolo's lab will have to report to OICR quarterly, it's a condition of the funding which is spread over two years and has the possibility of renewal for another two years.

"(It's) a lot more intense than I anticipated, but I think the key here is it's very results oriented," said Spagnuolo, "There's no complacency here."

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Pitting avocados against leukemia stem cells - CBC.ca

Bone Marrow Stem Cells Comments Off on Pitting avocados against leukemia stem cells – CBC.ca | June 6th, 2017

RenovaCare is developing breakthrough technologies to address Americas $45 billion wound and burn treatment market. Our flagship CellMist System makes use of a patients own stem cells, which are sprayed onto wounds using our novel SkinGun device.

For patients suffering severe burns and other wounds, the prospect of a quick-healing, gentle spray containing their own stem cells will be a promising alternative to conventional skin graft surgery, which can be painful, prone to complications, and slow-to-heal. Based on preliminary case studies, CellMist System patients can be treated within 90 minutes of arriving in an emergency room; a patients stem cells are isolated, processed, and sprayed on to wound sites for rapid healing.

Preliminary investigational use in Europe and the United States indicate the potential efficacy and safety of RenovaCares technologies. Clinical observations point to the potential for regeneration of new skin in as little as four days, rather than the many weeks of painful and risky recovery required by traditional skin graft techniques. These technologies are the result of nearly a decade of ongoing research and development dedicated to finding the most effective way to access the regenerative properties of a patients own skin stem cells, and the most efficient way to deliver these potent cells to heal moderate to severe skin wounds. We believe that RenovaCares CellMist System and SkinGun spray device are the worlds most advanced technologies of their kind.

This device system requires further clinical evaluation and data collection prior to submission of a premarketing application to the US FDA. At this time it is an investigational system and is not available for general use or sales in the United States.

The CellMist System RenovaCares CellMist System is comprised of two components:

Wikipedia indicates that so far the skin gun treatment has been used exclusively with second degree burns, though there is strong evidence that the treatment will be successful in treating a variety of skin wounds and skin disorders. Patients with infected wounds or with delay in wound healing are suitable for cell grafting treatment. Third-degree burns, however, completely deprive victims of both their epidermis and dermis skin levels, which exposes the tissue surrounding the muscles. The skin gun has not progressed to the point where it can be used for such advanced wounds, and these patients must seek more traditional treatment methods. The skin gun is generally not used for burn victims with anything less than a second-degree burn either. First degree-burns still maintain portions of the epidermis and can readily heal on their own, thus they do not need this expensive technology.

Currently, the skin guns applications have not been extended to include the regeneration of skin lost due to other injuries or skin diseases. It is also limited in that it is only effective immediately following the burn incident.

The average healing time for patients with second degree burns is three to four weeks. This is reduced to a matter of days with skin gun treatment

Traditional skin grafting can be risky, in that chances for infection are relatively high. The skin gun alleviates this concern because the increased speed in which the wound heals directly correlates to the decreased time the wound can be vulnerable to infection. Because of the rapid re-epithelialization associated with skin gun treatment, harmful side effects that can result from an open wound are significantly reduced. Applying the skin cells is quick and doesnt harm the patient because only a thin layer of the patients healthy skin is extracted from the body into the aqueous spray. The electronic spray distributes the skin cells uniformly without damaging the skin cells, and patients feel as if they are sprayed with salt water.

Because the skin cells are actually the patients own cells, the skin that is regenerated looks more natural than skin grown from traditional methods. During recovery, the skin cells grow into fully functional layers of the skin, including the dermis, epidermis, and blood vessels.[17] The regenerated skin leaves little scarring. The basic idea of optimizing regenerative healing techniques to damaged biological structures demonstrated by the skin gun in the future may also be applied to engineering reconstruction of vital organs, such as the heart and kidneys.

There are major limitations: the method will not work on deep burns that go through bone and muscle, specifically below the dermis. As of 2011, only several dozen patients have been treated; it remains an experimental, not a proven, method. As of 2011, the skin gun was still in its prototyping stage, since it has only treated a dozen patients in Germany and the US, compared to over 50,000 treated with Dermagraft bioengineered skin substitute. There is thus a lack of published peer reviewed clinical evidence, and no knowledge of long-term stability of the newly generated skin

Skingun Procedure

There is a seven page review of the skingun at the International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

Skingun Procedure Initially stamp-sized healthy skin of the injured patient is taken and stem cells were collected from it. Then they are harvested by using suitable enzymes. The prepared cell suspension is injected into sterile syringe and inserted into the gun. This gun helps in uniform spreading of the cells on wound. These cells will migrate, multiple, and differentiate forming a new tissue. The complete process occurs with in 2 hr. Full regeneration of skin occurs in 2 weeks and complete formation of texture tools 2-3 months

Stage 1

The CellMist Solution is a liquid suspension containing a patients own regenerative skin stem cells. A small sample (as little as a square inch) of the patients skin is quickly processed to liberate the stem cells from surrounding tissue. The resulting product is referred to as the CellMist Solution. The CellMist Solution is placed in the SkinGun for spray application onto the patients wound.

The CellMist Solution, containing the patients stem cells, is transferred to the SkinGun. The SkinGun sprays the cells onto wound sites to begin healing. Unlike conventional aerosol and pump systems, our next-generation fluid sprayer does not expose fragile cells to strong forces that can tear them apart. Instead our SkinGun gently delivers the CellMist Solution directly to the wound site using a positive-pressure air stream.

SOURCES RenovaCare, Wikipedia, International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

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Stem cells delivered via Skin gun can reduce second degree ...

Skin Stem Cells Comments Off on Stem cells delivered via Skin gun can reduce second degree … | June 6th, 2017

New skin begins to regenerate as soon as 4 days after this has been sprayed on patients, compared to skin grafting surgery which may take weeks of pain and possible infections.

Patients who suffer from burn wounds and scars that cant heal on their own only have 1 option: skin graft surgery. This can be very painful, and usually leads to several other complications, and it takes forever to actually heal.

However, RenovaCare has developed a new breakthrough piece of tech: CellMist, a gun that sprays stem cells into a patients burn wound, effectively allowing healthy skin to grow out of it.

It works literally like we described it as. Within 90 minutes of a patient being brought to the emergency room, they stem cells are isolated, processed, put in a liquid suspension, and then loaded into the CellMist gun. CellMist then gently sprays the stem cells onto the patients burn wound.

Tests conducted in Europe and the US have shown that new skin begins to regenerate as soon as 4 days after its been sprayed on patients, compared to skin grafting surgery which may take weeks of pain and possible infections.

Source: Next Big Future

So far, CellMist has only been used to treat second degree burns. However, evidence has shown that it can be used for other skin wounds and skin disorders. They dont think itll work for third degree burns though, as this kind of burn wound has damaged the entire epidermis and dermis levels. CellMist isnt advanced enough to heal such a deep burn wound, and victims would unfortunately have to stick to more traditional methods of treatment. First degree burn wounds on the other hand only barely touch the epidermis, meaning it can still heal on its own, thus not needing such an expensive piece of technology.

It is good to note that even though there is evidence that it might be able to heal things other than burns, CellMist wasnt built to regenerate skin lost from other kinds of injuries or diseases. Its also pretty limited, because as we stated earlier, it should be used immediately after the burn incident has occurred, or else it wont work.

Its still a pretty handy invention. The reason why skin grafting is so risky is because it involves cutting the skin open and leaving it open for 3-4 weeks. This means that nasty bacteria and fungi can easily get into the open wound within that time, causing several infections and complications.

Source: Next Big Future

With CellMist, however, simply involves extracting a thin layer of the patients healthy skin and stem cells and turning it into a spray, and then distributing the stem cells into the burn wound evenly, without damaging other healthy skin cells. The healing time only takes a few days, so there is little chance for an infection to occur if treated properly. And since the patients own skin cells are used in the process, the regenerated skin looks much more natural, with only little scarring. The stem cells grow into fully functioning layers of skin, from the dermis, to the epidermis, to even blood vessels.

Hopefully, this cool new invention will make way for other forms of stem cell treatments for the reconstruction of other organs, like ones heart and kidneys.

Article Sources:

Deccan Chronicle

Next Big Future

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This Stem Cell Gun Helps Burn Victims Grow New Skin Faster - GineersNow (press release) (registration) (blog)

Skin Stem Cells Comments Off on This Stem Cell Gun Helps Burn Victims Grow New Skin Faster – GineersNow (press release) (registration) (blog) | June 6th, 2017