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

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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

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

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

COUNTLESS lives across the world could be saved by an Oxfordshire familys appeal to find a bone marrow donor for their little boy.

Two-year-old Alastair Ally Kim has Chronic Granulomatous Disorder (CGD), a life-threatening condition.

He has now become the fourth person in the world to start an experimental gene therapy course at Great Ormond Street Hospital.

In the meantime, his parents have spearheaded 200 international donor drives to find their son a match, signing up 7,000 would-be donors in the process - some of whom have since been matched with other patients.

Father Andrew Kim, 37, of Hinton Waldrist near Longworth, said: We want to use whatever momentum Allys story has to help someone else. We know that matches have come through our drives for other people. Its awesome that someone will benefit from all this.

On Thursday, May 25 family friend Cathy Oliveira organised a drive at the Oxford Universitys Old Road research building, signing up 80 staff members in a day.

Ms Oliveira said: When everything happened with Ally I wanted to show support in any way we could; this is directly beneficial not just for Ally but for others.

Allys CGD means his immune system is compromised and the tiniest infection could leave him seriously ill.

His only chance of a permanent cure is a bone marrow stem cell donation, with a match likely to be of Korean or East Asian origin.

In April the youngster and mum Judy Kim, 36, an Oxford University researcher, travelled to London for him to begin a pioneering new gene therapy treatment.

After a week of chemotherapy to wipe out Allys immune system, cells taken from him are modified in a lab and re-introduced to correct the disorder.

Mr Kim said: Bone marrow would give him back 100 per cent functionality and gene therapy is 10 to 15 per cent; its enough to live in the real world, and not be scared he will die every time he gets an infection.

It has been a roller-coaster of a year, but theres nothing to do but move forward. We are really excited at the thought of him being able to come home this summer.

Blood cancer charity DKMS supported last weeks donor drive in Oxford.

Senior donor recruitment manager Joe Hallet said: Around 30 per cent of patients in need of a blood stem cell donor will find a matching donor within their own family.

The remaining 70 per cent, like Ally, will need to find an unrelated donor to have a second chance of life, so events like these are crucial.

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Oxford University staff join bone marrow stem cell donor drive for Oxford toddler Ally Kim - Witney Gazette

Bone Marrow Stem Cells Comments Off on Oxford University staff join bone marrow stem cell donor drive for Oxford toddler Ally Kim – Witney Gazette | June 3rd, 2017

In BriefBioquark is about to begin a trial that will attempt to bringbrain-dead patients back to life using stem cells. However, thetrial is raising numerous scientific and ethical questions forother experts in the field. Back From The Dead

Researchers seem to be setting their sights on increasinglylofty goals when it comes to the human body from the worlds first human head transplant, to fighting aging, and now reversing death altogether. Yes, you read that right. A company called Bioquarkhopes to bring people who have been declared clinically brain-dead back to life. The Philadelphia-based biotech company is expected to start on the project later this year.

This trial was originally intended to go forward in 2016 in India, but regulators shut it down. Assuming this plan will be substantially similar, it will enroll 20 patients who will undergo various treatments. The stem cell injection will come first, with the stem cells isolated from that patients own blood or fat. Next, the protein blend gets injected directly into the spinal cord, which is intended to foster growth of new neurons. The laser therapy and nerve stimulation follow for 15 days, with the aim of prompting the neurons to make connections. Meanwhile, the researchers will monitor both behavior and EEGs for any signs of the treatment causing any changes.

While there is some basis in science for each step in the process, the entire regimen is under major scrutiny. The electrical stimulation of the median nerve has been tested, but most evidence exists in the form of case studies. Dr. Ed Cooper has described dozens of these cases, and indicates that the technique can have some limited success in some patients in comas. However, comas and brain death are very different, and Bioquarks process raises more questions for most researchers than it answers.

One issue researchers are raising about this study is informed consent. How can participants in the trial consent, and how should researchers complete their trial paperwork given that the participants are legally dead and how can brain death be conclusively confirmed, anyway? What would happen if any brain activity did return, and what would the patients mental state be? Could anything beyond extreme brain damage even be possible?

As reported by Stat News, In 2016, neurologist Dr. Ariane Lewis and bioethicist Arthur Caplan wrote in Critical Care that the trial is dubious, has no scientific foundation, and suffers from an at best, ethically questionable, and at worst, outright unethical nature. According to Stat News, despite his earlier work with electrical stimulation of the median nerve, Dr. Cooper also doubts Bioquarks method, and feels there is no way this technique could work on someone who is brain-dead. The technique, he said, relies on there being a functional brain stem one of the structures that most motor neurons go through before connecting with the cortex proper. If theres no functional brain stem, then it cant work.

Pediatric surgeon Charles Cox, who is not involved in Bioquarks work, agrees with Cooper, commenting to Stat News on Bioquarks full protocol, its not the absolute craziest thing Ive ever heard, but I think the probability of that working is next to zero. I think [someone reviving] would technically be a miracle.

Pastor remains optimistic about Bioquarks protocol. I give us a pretty good chance, he said. I just think its a matter of putting it all together and getting the right people and the right minds on it.

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Scientists Hope to Use Stem Cells to Reverse Death in ... - Futurism - Futurism

Spinal Cord Stem Cells Comments Off on Scientists Hope to Use Stem Cells to Reverse Death in … – Futurism – Futurism | June 2nd, 2017

Seven drugs of the current top-10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products.

Dr Subir Basak Chief Business Officer, GVK Biosciences

Over the last two decades, the Pharmaceutical industry has seen a radical change. The unprecedented downsizing of the internal discovery of big pharmaceuticals, patent expiration, shift towards biologics have seen a surge in the externalization and outsourcing activities. As the industry is looking for new sources of discovery and innovation with limited resources, there is a growing preference to move towards externalization and willingness to embrace the concept of outsourcing.

Seven drugs of the current top- 10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products. Global R&D spend in the biopharmaceutical industry is estimated to be $194 billion in 2016 and according to industry experts, 75-80% of the expenses can be outsourced. However, current penetration rate is around 58% which presents a huge opportunity for the CROs to tap the Trends in Drug Discovery Outsourcing: A Perspective market. The global pharmaceutical outsourcing market was estimated to be $113.7 billion in 2016 and out of which 49% is accounted for CROs. Among the $55.7 billion CRO market, 31.2% accounts for discovery-based service i.e. $17.4 billion in 2016 and the remaining 68.8% accounts for Preclinical and clinical services.

Biology related services segment is a high growth area with huge potential and expected to grow faster at a CAGR of 17.2% compared to the small molecules segment due to increase in budget allocations for R&D by biopharmaceutical companies.

The drug discovery CRO industry is witnessing increased consolidation. Many Asia-based companies are increasing their foothold in Europe and North America. GVK BIO, a Contract Research & Development Organization (CRDO) from India has taken over Aragen Bioscience. Aragen has early stage discovery biologics capabilities and played a leading role in oncology and fibrosis based animal models for preclinical biotechs in bay area. Similarly, ChemPartner established research facility in South San Francisco. Also, WuXi AppTec acquired HD Biosciences (HDB), a biology focused preclinical drug discovery CRO.

Advancement in drug discovery technologies such as iPS cells, automated high content screening, patch clamp, gene editing and DNAencoded libraries have expedited the drug discovery process with increased efficiency. There is an increased interest in the use of DNAencoded libraries (small molecules tagged with DNAs) by major pharma companies.Majority of the companies offering DNA-encoded library services are from US (DiCE, X-Chem, Ensemble therapeutics) and Europe (Nuevolution, Vipergen, Cominnex, Philochem). Thereseems to be very little competition in APAC. This trend should push some of the CROs from APAC region to acquire companies with proprietary technology in DNA-encoded libraries or to build capabilities and this seems likely to be a focus point for majority of the CROs especially from APAC.

Evolving business models including risk-based and insourcing are facilitating better collaboration between pharmaceutical companies and CROs. Some of the companies established a new business model known as insourcing which is a new sourcing for pharma where CROs work on-site at customer location in an integrated fashion. This new model provides outstanding performance with efficient cost and time.

CROs should build capabilities to differentiate in the area of Target Identification/Target Validation on how to use human disease pathology knowledge/primary tissues from humans clubbed with Omics knowledge to further validate the concepts. As most of the CROs propose targets from literature and sponsor companies consider it as risky option to invest in such projects without substantial evidences. As a de-risking strategy some CROs are investing internally and validating the concept by siRNA, knockdown approaches and take the concept to a level-up and then approach the sponsors companies who are working in similar area. This approach would increase the sponsor confidence in the CRO program.

There is a huge demand for the novel therapeutics addressing the unmet needs, for example, there are no FDA approved drugs or any therapies for NASH treatment and there is a tremendous opportunity for CROs to work on novel targets, preclinical models and biomarker to come-up with some early stage assets for partnering. Owing to market attractiveness, there is funding provided by venture capitalists to promising players, while some investors are even launching new companies to specifically work on NASH projects. For instance in February 2017, Versant Ventures formed Jecure Therapeutics through $20 million investment for NASH program development. Similarly, Third Rock Ventures formed Pliant Therapeutics with $45 million investment for TGF- signaling based NASH treatment. These companies could potentially outsource majority of the work to CROs in APAC region.

Asia is emerging as a preferred destination for outsourcing drug discovery activities due to the vast availability of skilled manpower, lower costs, favorable regulatory environment and quality data. In addition the local governments are focusing on development of healthcare and pharmaceutical industryby ensuring focus on high quality & compliance in terms of higher regulatory surveillance and training programs. Japan being the second largest pharmaceutical market in the world provides huge opportunity for CROs from APAC. Chinese and Indian pharmaceutical markets are one of the fastest growing in the world and are considered to be the preferred locations for drug discovery outsourcing primarily because of the end-to-end technological capabilities developed over several years. Asian CROs have strong capabilities in biologics research services and built new technology platforms for high-throughput screening, genomics and proteomics research panel screening, enzymatic, and binding assays. They are also well equipped with transgenic and disease animal models that have been developed for target validation, efficacy, and safety studies, thereby providing clients with end-to-end services. Indian CROs typically focus more on new chemical entities and offer integrated discovery services at much lower cost.

Therapeutic area gap analysis research indicates that the key contract research organizations in Asia pacific region are majorly focusing on Oncology, metabolic diseases, Inflammation and CNS. However, majority of Pharma companies in addition to the above therapeutic areas are also focusing on other areas like cardiovascular, immunology, infectious diseases. Since there is a high gap in these therapeutic areas, the CROs should increase their focus in order to tap the opportunity.

Growth in biologics research and orphan drugs, innovative technological platforms and evolving business models encourage pharma and biotech companies to outsource. Even though, big pharma is moving towards research institutions and academia to accelerate knowledge and leverage innovation and technology platforms, they lack the infrastructure to move the drugs from early stages of drug discovery. These factors are expected to enhance drug discovery outsourcing market in APAC region for the coming years.

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Trends in Drug Discovery Outsourcing: A Perspective - BSA bureau (press release)

IPS Cell Therapy Comments Off on Trends in Drug Discovery Outsourcing: A Perspective – BSA bureau (press release) | June 2nd, 2017

In experiments in mice, UC San Francisco researchers have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell generally associated with controlling inflammation,directly trigger stem cells in the skin to promote healthy hair growth. Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back, saidMichael Rosenblum, M.D., an assistant professor of dermatology at UCSF and senior author on the new paper. This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

The new study published online May 26 inCell suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said. Since the same stem cells are responsible for helping heal the skin after injury, the study raises the possibility that Tregs may play a key role in wound repair as well.

Normally Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, we may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help with wound healing into adulthood.

Rosenblum, who is both an immunologist and a dermatologist, wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery. We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

In the new research, led by UCSF postdoctoral fellow and first authorNiwa Ali,several lines of evidence suggested that Tregs play a role in triggering hair follicle regeneration.

First, imaging experiments revealed that Tregs have a close relationship with the stem cells that reside within hair follicles and allow them to regenerate: the number of active Tregs clustering around follicle stem cells typically swells by three-fold as follicles enter the growth phase of their regular cycle of rest and regeneration. Also, removing Tregs from the skin blocked hair regrowth only if this was done within the first three days after shaving a patch of skin, when follicle regeneration would normally be activated. Getting rid of Tregs later on, once the regeneration had already begun, had no effect on hair regrowth.

Tregs role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation, the researchers found. Instead, they discovered that Tregs trigger stem cell activation directly through a common cell-cell communication system known as the Notch pathway. First, the team demonstrated that Tregs in the skin express unusually high levels of a Notch signaling protein called Jagged 1 (Jag1), compared to Tregs elsewhere in the body. They then showed that removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein restored Notch signaling in the stem cells and successfully activated follicle regeneration.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work, Rosenblum said. Now the stem cells rely on the Tregs completely to know when its time to start regenerating.

Rosenblum said the findings may have implications for alopecia areata, an autoimmune disease that interferes with hair follicle regeneration and causes patients to lose hair in patches from their scalp, eyebrows, and faces. Alopecia is among the most common human autoimmune diseases its as common as rheumatoid arthritis, and more common than type 1 diabetes but scientists have little idea what causes it.

After his team first observed hair loss in Treg-deficient mice, Rosenblum learned that the genes associated with alopecia in previous studies are almost all related to Tregs, and treatments that boost Treg function have been shown to be an effective treatment for the disease. Rosenblum speculates that better understanding Tregs critical role in hair growth could lead to improved treatments for hair loss more generally.

The study also adds to a growing sense that immune cells play much broader roles in tissue biology than had previously been appreciated, said Rosenblum, who plans to explore whether Tregs in the skin also play a role in wound healing, since the same follicle stem cells are involved in regenerating skin following injury.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after its damaged, he said. But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

Niwa Aliof UCSF was the lead author on the new study. Additional authors were Bahar Zirak,Robert Sanchez Rodriguez, Mariela L. Pauli,Hong-An Truong, Kevin Lai,Richard Ahn, Kaitlin Corbin, Margaret M. Lowe, PharmD,Tiffany C. Scharschmidt, M.D., Keyon Taravati, Madeleine R. Tan,Roberto R. Ricardo-Gonzalez, M.D., Audrey Nosbaum, M.D.,Wilson Liao, M.D., andAbul K. Abbas, MBBS, of UCSF; Frank O. Nestle, M.D., of Kings College London; Marta Bertoliniand Ralf Paus, M.D., of the University of Mnster in Germany; and George Cotsarelis, M.D., of the University of Pennsylvanias Perelman School of Medicine.

The work was primarily supported by the U.S. National Institutes of Health (K08-AR062064, DP2-AR068130, R21-AR066821), the Burroughs Wellcome Fund, a Scleroderma Research Foundation grant, the National Psoriasis Foundation and the Dermatology Foundation.

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A new baldness treatment? | University of California - University of California

Skin Stem Cells Comments Off on A new baldness treatment? | University of California – University of California | June 2nd, 2017

Jaime Berg, KUSA 3:00 PM. MDT May 31, 2017

Source: University of Colorado

KUSA - A SpaceX rocket is scheduled to launch Thursday -- and on board will be two payloads built by researchers at the University of Colorado in Boulder. The payloads include studies that could be life-changing for people on earth.

One of the experiments involves cardiovascular stem cells. The work is with some researchers in California.

Theyre investigating how gravity affects stem cells, including physical and molecular changes. The information, could help lead to stem cell therapies to repair damaged cardiac tissue.

One of the experiments has to do with rodents.

Mice are actually being sent to the international space station, in a NASA habitat, designed for spaceflight.

The mice will be going through a series of experiments to study bone loss in space.

The experiments will be sent in shoebox sized habitats.

Both undergrad and graduate students at CU are involved in the research efforts.

2017 KUSA-TV

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SpaceX rocket will be carrying CU experiments - 9NEWS.com

Cardiac Stem Cells Comments Off on SpaceX rocket will be carrying CU experiments – 9NEWS.com | May 31st, 2017

These photomicrographs show the initial scratches created with a pipette tip compared with the same scratch 36 hours later and at end of study, at 72 hours, for each experimental group. ac show the control group, from left, at the start, after 36 hours, and after 72 hours. df show the results for the same horse with use of the supernatant solution; and gi show the results for the same horse from the stem cell group. Images: Sherman et al DOI: 10.1186/s13287-017-0577-3

Stem cells taken from bone marrow may substantially improve corneal wound healing in horses, evidence from a study suggests.

Eye injuries are common in horses, most likely because of the size of their eyes and their prominent position in the head.

Researchers from the North Carolina State University College of Veterinary Medicine conducted a laboratory experiment to assess the performance of stem cells taken from bone marrow in the breast bone of five horses.

Amanda Sherman and her colleagues, writing in Stem Cell Research & Therapy, described the process by which they collected and isolated the autologous bone marrow-derived mesenchymal stem cells for their study.

Mesenchymal stem cells are multipotent connective-tissue cells that can change into a variety of cell types to form the likes of bone, cartilage, muscle and fat.

The supernatant solution comprising cell-medium sediment left over from the centrifuging process was also used in the study to compare its performance against the stem cells. A naive culture media was used as a control.

Corneal stromal cells were cultured and transferred on to six collagen-coated plates. A scratch was then placed the length of these equine corneal fibroblast cultures using a fine pipette.

The plates were then exposed to either the stem cells, the supernatant solution or the naive culture medium.

The researchers reported a significant percentage decrease in the scratch area remaining in the stem cell and supernatant groups compared to the control group after 72 hours.

The decrease was significantly greater in the stem-cell group compared to the supernatant group 36 hours after exposure and at all times thereafter.

The performance of the supernatant solution was most likely due to the presence of the growth factor TGF-1, which was identified on analysis. TGF-1 was found in even greater concentrations in the stem cell group.

The researchers concluded that the use of autologous bone marrow-derived mesenchymal stem cells may substantially improve corneal wound healing in horses.

The supernatant solution may also improve corneal wound healing, given the significant decrease in scratch area compared to control treatments, and would be an immediately available and cost-effective treatment option, they said.

The researchers said studies in live horses were warranted to evaluate the potential treatments safety and effectiveness for corneal wound healing.

The universitys study team comprised Sherman,Brian Gilger,Alix Berglund and Lauren Schnabel.

Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro Amanda B. Sherman, Brian C. Gilger, Alix K. Berglund and Lauren V. Schnabel Stem Cell Research & Therapy 2017 8:120 DOI: 10.1186/s13287-017-0577-3

The study, published under a Creative Commons License, can be read here.

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Stem cells show promise in helping to heal eye injuries in horses ... - Horsetalk

Bone Marrow Stem Cells Comments Off on Stem cells show promise in helping to heal eye injuries in horses … – Horsetalk | May 30th, 2017

By By Elianna Novitch, The Gazette

May 29, 2017 at 5:00 am | Print View

IOWA CITY More than 20 million people are registered as bone marrow donors in the Be the Match registry, the largest and most diverse donor registry in the world.

But none can help Calder Wills, a 12-year-old Iowa City boy battling stage 4 T-cell lymphoma, or cancer of the blood.

Only one person has been identified as a 100-percent match for Calder, but that person was deemed medically unable to donate bone marrow.

This has left the Wills family with few options.

And so, friends of the family are hosting a donor registry drive on Tuesday to raise awareness about the need for more marrow donors and to perhaps find a match for Calder and others like him.

The event takes place from 3 to 8 p.m. inside the gym at Hoover Elementary School, 2200 E. Court St., Iowa City. Those who attend can join the Be The Match registry. Those who are unable to attend can register online at bethematch.org.

Calder was diagnosed with lymphoma in February 2016. He went into remission within the first 30 days but found out on April 11 the day after his 12th birthday that he had relapsed and would need a bone-marrow transplant. He is one of thousands searching for a match.

He is among the 70 percent of patients who surprisingly dont have a match in their own family, explained Colleen Reardon, manager of the Iowa Marrow Donor Program at the University of Iowa Hospitals & Clinics. We are looking for a tissue type match and each sibling has about a 25 percent chance of being a match.

Calder has three siblings, a twin brother Grayson and sisters Charlotte, 7, and Arden, 5, all of whom were not matches. The next best chance a patient has, statistically, is to find an unrelated donor that is a 100-percent match.

Calders mother Brianna Wills described it as devastating when the family found out that the 58-year-old woman who matched with Calder was deemed medically unable to donate.

That left us with no match, no options, she said. Weve decided to pursue cord blood for his transplant, Wills said. He is going to have a cord blood transplant at the University of Minnesota because a bone marrow match wasnt available and he couldnt wait until one became available.

According to the Be The Match website, cord blood is one of three sources of blood-forming cells used in transplant. The others are bone marrow and peripheral blood stem cells. Cord blood can be used to treat more than 80 diseases, including blood cancers like leukemia and lymphoma. Cord blood comes from a babys umbilical cord.

Wills said that even though Calder is receiving a different type of transplant, she does not want people to not register as a marrow donor.

I dont want that to dissuade people from continuing to do it because he has about a two out of three chance that this transplant will fail because he has T-cell lymphoma that is very aggressive and very hard to treat, Wills said. Realistically, statistically, we are looking at him needing a second transplant down the road and thats when we hope that well find a donor and we can use a bone marrow match then.

Please still do it and not just for Calder, do it for the thousands of people who also dont have a match.

According to Reardon, of every 540 people who register as a donor, only one will be identified as that perfect match for someone and be asked to donate.

Were not realistically hoping to find Calders donor, I mean that would be amazing, but really were hoping to expand the database. Were just hoping that some family in Texas or somewhere else in the world is also doing this and maybe theyll find Calders donor, Wills said. If were all doing it, were going to expand the database for everyones benefit.

Wills recognizes that even though the drive is in Calders honor, it is truly to the benefit of thousands of other people who dont have donors.

There are other ethnic groups that have very little participation and to be a match you need to be matched with donors that have similar ethnic background as you do, Wills said. So African Americans, Hispanics, people that have mixed races, or Asian background wed love to have them come because there are people waiting for donors of all kinds of backgrounds.

What: Bone Marrow Donor Drive

When: 3 to 8 p.m. Tuesday

Where: Hoover Elementary School, 2200 E. Court St., Iowa City

Details: Join the Iowa Marrow Donor Program and Be The Match Registry using a simple cheek swab.

Info: join.bethematch.org/CalderStrong or call the Iowa Marrow Donor Program at (319) 356-3337.

l Comments: (319) 368-8538; elianna.novitch@thegazette.com

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Bone marrow donor drive honors Iowa City boy battling lymphoma ... - The Gazette: Eastern Iowa Breaking News and Headlines

Bone Marrow Stem Cells Comments Off on Bone marrow donor drive honors Iowa City boy battling lymphoma … – The Gazette: Eastern Iowa Breaking News and Headlines | May 29th, 2017

A new cause of baldness has been accidentally discovered by scientists in the US in a breakthrough that could help develop a way to regrow hair.

The researchers were investigating the role played by anti-inflammatory immune cells called Tregs in skin health generally.

They found a way to temporarily remove the Tregs from the skin of laboratory mice, who had been shaved to allow the effects to be observed.

But the scientists then noticed something unexpected the hairfailed to grow back.

Previously it was thought that stem cells cause hairs to regrow after they fall out, but the team discoveredthat this only happens if Tregs are present.

One of the scientists, Professor Michael Rosenblum, an immunologist and dermatologist at University of California San Francisco, said: Our hair follicles are constantly recycling. When a hair falls out, the whole hair follicle has to grow back.

This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential.

If you knock out this one immune cell type, hair just doesn't grow.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work.

The stem cells rely on the Tregs completely to know when it's time to start regenerating.

The researcher believe that defects in Tregs could be responsible for the immune disease, alopecia areata, which causes hair to fall out in patches and possibly also play a part in other kinds of baldness.

The same stem cells that regrow hair are also involved in healing damage to the skin, so Tregs may also be involved in this process.

Tregs role as previously understood was mainly to regulate the immune system, helping it tell what to attack and what to leave alone.

When they malfunction it can lead to allergies to peanuts and other harmless substances or cause the immune system to attack the body.

Professor Rosenblum and colleagues had previously showed that Tregs help the immune systems of baby mice learn which skin microbes are not harmful and also that they secrete molecules that help heal wounds.

They were investigating these effects further when they noticed that patches of shaved hair on the lab mice were not regrowing.

We thought, Hmm, now thats interesting, Professor Rosenblum said. We realised we had to delve into this further.

Using sophisticated imaging techniques, the researchers were able to show that Tregs gathered around follicle stem cells at the start of the process to regrow a hair.

When Tregs were removed from the skin, this prevented the regrowth of hair but only if this was done within three days of the hair being shaved. After this time, the hair would regrow normally despite the absence of Tregs.

The cause of alopecia is poorly understood, but previous studies have showed genes associated with the condition are mostly related to Tregs. Boosting Treg function has been found to help.

Professor Rosenblum suggested further research into Tregs role could lead to improved treatments for hair loss generally and better understanding of their role in wound healing.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after it's damaged, he said.

But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

The research was described in the journal Cell.

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New baldness cause accidentally discovered by scientists could lead to hair loss treatment - The Independent

Skin Stem Cells Comments Off on New baldness cause accidentally discovered by scientists could lead to hair loss treatment – The Independent | May 25th, 2017

On a cold, bright January morning I walked south across Westminster Bridge to St Thomas Hospital, an institution with a proud tradition of innovation: I was there to observe a procedure generally regarded as the greatest advance in cardiac surgery since the turn of the millennium and one that can be performed without a surgeon.

The patient was a man in his 80s with aortic stenosis, a narrowed valve which was restricting outflow from the left ventricle into the aorta. His heart struggled to pump sufficient blood through the reduced aperture, and the muscle of the affected ventricle had thickened as the organ tried to compensate. If left unchecked, this would eventually lead to heart failure. For a healthier patient the solution would be simple: an operation to remove the diseased valve and replace it with a prosthesis. But the mans age and a long list of other medical conditions made open-heart surgery out of the question. Happily, for the last few years, another option has been available for such high-risk patients: transcatheter aortic valve implantation, known as TAVI for short.

This is a non-invasive procedure, and takes place not in an operating theatre but in the catheterisation laboratory, known as the cath lab. When I got there, wearing a heavy lead gown to protect me from X-rays, the patient was already lying on the table. He would remain awake throughout the procedure, receiving only a sedative and a powerful analgesic. I was shown the valve to be implanted, three leaflets fashioned from bovine pericardium (a tough membrane from around the heart of a cow), fixed inside a collapsible metal stent. After being soaked in saline it was crimped on to a balloon catheter and squeezed, from the size and shape of a lipstick, into a long, thin object like a pencil.

The consultant cardiologist, Bernard Prendergast, had already threaded a guidewire through an incision in the patients groin, entering the femoral artery and then the aorta, until the tip of the wire had arrived at the diseased aortic valve. The catheter, with its precious cargo, was then placed over the guidewire and pushed gently up the aorta. When it reached the upper part of the vessel we could track its progress on one of the large X-ray screens above the table. We watched intently as the metal stent described a slow curve around the aortic arch before coming to rest just above the heart.

There was a pause as the team checked everything was ready, while on the screen the silhouette of the furled valve oscillated gently as it was buffeted by pulses of high-pressure arterial blood. When Prendergast was satisfied that the catheter was precisely aligned with the aortic valve, he pressed a button to inflate the tiny balloon. As it expanded it forced the metal stent outwards and back to its normal diameter, and on the X-ray monitor it suddenly snapped into position, firmly anchored at the top of the ventricle. For a second or two the patient became agitated as the balloon obstructed the aorta and stopped the flow of blood to his brain; but as soon as it was deflated he became calm again.

Prendergast and his colleagues peered at the monitors to check the positioning of the device. In a conventional operation the diseased valve would be excised before the prosthesis was sewn in; during a TAVI procedure the old valve is left untouched and the new one simply placed inside it. This makes correct placement vital, since unless the device fits snugly there may be a leak around its edge. The X-ray picture showed that the new valve was securely anchored and moving in unison with the heart. Satisfied that everything had gone according to plan, Prendergast removed the catheter and announced the good news in a voice that was probably audible on the other side of the river. Just minutes after being given a new heart valve, the patient raised an arm from under the drapes and shook the cardiologists hand warmly. The entire procedure had taken less than an hour.

According to many experts, this is what the future will look like. Though available for little more than a decade, TAVI is already having a dramatic impact on surgical practice: in Germany the majority of aortic valve replacements, more than 10,000 a year, are now performed using the catheter rather than the scalpel.

In the UK, the figure is much lower, since the procedure is still significantly more expensive than surgery this is largely down to the cost of the valve itself, which can be as much as 20,000 for a single device. But as the manufacturers recoup their initial outlay on research and development, it is likely to become more affordable and its advantages are numerous. Early results suggest that it is every bit as effective as open-heart surgery, without many of surgerys undesirable aspects: the large chest incision, the heart-lung machine, the long period of post-operative recovery.

The essential idea of TAVI was first suggested more than half a century ago. In 1965, Hywel Davies, a cardiologist at Guys Hospital in London, was mulling over the problem of aortic regurgitation, in which blood flows backwards from the aorta into the heart. He was looking for a short-term therapy for patients too sick for immediate surgery something that would allow them to recover for a few days or weeks, until they were strong enough to undergo an operation. He hit upon the idea of a temporary device that could be inserted through a blood vessel, and designed a simple artificial valve resembling a conical parachute. Because it was made from fabric, it could be collapsed and mounted on to a catheter. It was inserted with the top of the parachute uppermost, so that any backwards flow would be caught by its inside surface like air hitting the underside of a real parachute canopy. As the fabric filled with blood it would balloon outwards, sealing the vessel and stopping most of the anomalous blood flow.

This was a truly imaginative suggestion, made at a time when catheter therapies had barely been conceived of, let alone tested. But, in tests on dogs, Davies found that his prototype tended to provoke blood clots and he was never able to use it on a patient.

Another two decades passed before anybody considered anything similar. That moment came in 1988, when a trainee cardiologist from Denmark, Henning Rud Andersen, was at a conference in Arizona, attending a lecture about coronary artery stenting. It was the first he had heard of the technique, which at the time had been used in only a few dozen patients, and as he sat in the auditorium he had a thought, which at first he dismissed as ridiculous: why not make a bigger stent, put a valve in the middle of it, and implant it into the heart via a catheter? On reflection, he realised that this was not such an absurd idea, and when he returned home to Denmark he visited a local butcher to buy a supply of pig hearts. Working in a pokey room in the basement of his hospital with basic tools obtained from a local DIY warehouse, Andersen constructed his first experimental prototypes. He began by cutting out the aortic valves from the pig hearts, mounted each inside a home-made metal lattice then compressed the whole contraption around a balloon.

Within a few months Andersen was ready to test the device in animals, and on 1 May 1989 he implanted the first in a pig. It thrived with its prosthesis, and Andersen assumed that his colleagues would be excited by his works obvious clinical potential. But nobody was prepared to take the concept seriously folding up a valve and then unfurling it inside the heart seemed wilfully eccentric and it took him several years to find a journal willing to publish his research.

When his paper was finally published in 1992, none of the major biotechnology firms showed any interest in developing the device. Andersens crazy idea worked, but still it sank without trace.

Andersen sold his patent and moved on to other things. But at the turn of the century there was a sudden explosion of interest in the idea of valve implantation via catheter. In 2000, a heart specialist in London, Philipp Bonhoeffer, replaced the diseased pulmonary valve of a 12-year-old boy, using a valve taken from a cows jugular vein, which had been mounted in a stent and put in position using a balloon catheter.

In France, another cardiologist was already working on doing the same for the aortic valve. Alain Cribier had been developing novel catheter therapies for years; it was his company that bought Andersens patent in 1995, and Cribier had persisted with the idea even after one potential investor told him that TAVI was the most stupid project ever heard of.

Eventually, Cribier managed to raise the necessary funds for development and long-term testing, and by 2000 had a working prototype. Rather than use an entire valve cut from a dead heart, as Andersen had, Cribier built one from bovine pericardium, mounted in a collapsible stainless-steel stent. Prototypes were implanted in sheep to test their durability: after two-and-a-half years, during which they opened and closed more than 100m times, the valves still worked perfectly.

Cribier was ready to test the device in humans, but his first patient could not be eligible for conventional surgical valve replacement, which is safe and highly effective: to test an unproven new procedure on such a patient would be to expose them to unnecessary risk.

In early 2002, he was introduced to a 57-year-old man who was, in surgical terms, a hopeless case. He had catastrophic aortic stenosis which had so weakened his heart that with each stroke it could pump less than a quarter of the normal volume of blood; in addition, the blood vessels of his extremities were ravaged by atherosclerosis, and he had chronic pancreatitis and lung cancer. Several surgeons had declined to operate on him, and his referral to Cribiers clinic in Rouen was a final roll of the dice. An initial attempt to open the stenotic valve using a simple balloon catheter failed, and a week after this treatment Cribier recorded in his notes that his patient was near death, with his heart barely functioning. The mans family agreed that an experimental treatment was preferable to none at all, and on 16 April he became the first person to receive a new aortic valve without open-heart surgery.

Over the next couple of days the patients condition improved dramatically: he was able to get out of bed, and the signs of heart failure began to retreat. But shortly afterwards complications arose, most seriously a deterioration in the condition of the blood vessels in his right leg, which had to be amputated 10 weeks later. Infection set in, and four months after the operation, he died.

He had not lived long nobody expected him to but the episode had proved the feasibility of the approach, with clear short-term benefit to the patient. When Cribier presented a video of the operation to colleagues they sat in stupefied silence, realising that they were watching something that would change the nature of heart surgery.

When surgeons and cardiologists overcame their initial scepticism about TAVI they quickly realised that it opened up a vista of exciting new surgical possibilities. As well as replacing diseased valves it is now also possible to repair them, using clever imitations of the techniques used by surgeons. The technology is still in its infancy, but many experts believe that this will eventually become the default option for valvular disease, making surgery increasingly rare.

While TAVI is impressive, there is one even more spectacular example of the capabilities of the catheter. Paediatric cardiologists at a few specialist centres have recently started using it to break the last taboo of heart surgery operating on an unborn child. Nowhere is the progress of cardiac surgery more stunning than in the field of congenital heart disease. Malformations of the heart are the most common form of birth defect, with as many as 5% of all babies born with some sort of cardiac anomaly though most of these will cause no serious, lasting problems. The heart is especially prone to abnormal development in the womb, with a myriad of possible ways in which its structures can be distorted or transposed. Over several decades, specialists have managed to find ways of taming most; but one that remains a significant challenge to even the best surgeon is hypoplastic left heart syndrome (HLHS), in which the entire left side of the heart fails to develop properly. The ventricle and aorta are much smaller than they should be, and the mitral valve is either absent or undersized. Until the early 1980s this was a defect that killed babies within days of birth, but a sequence of complex palliative operations now makes it possible for many to live into adulthood.

Because their left ventricle is incapable of propelling oxygenated blood into the body, babies born with HLHS can only survive if there is some communication between the pulmonary and systemic circulations, allowing the right ventricle to pump blood both to the lungs and to the rest of the body. Some children with HLHS also have an atrial septal defect (ASD), a persistent hole in the tissue between the atria of the heart which improves their chances of survival by increasing the amount of oxygenated blood that reaches the sole functioning pumping chamber. When surgeons realised that this defect conferred a survival benefit in babies with HLHS, they began to create one artificially in those with an intact septum, usually a few hours after birth. But it was already too late: elevated blood pressure was causing permanent damage to the delicate vessels of the lungs while these babies still in the womb.

The logical albeit risky response was to intervene even earlier. In 2000, a team at Boston Childrens Hospital adopted a new procedure to create an ASD during the final trimester of pregnancy: they would deliberately create one heart defect in order to treat another. A needle was passed through the wall of the uterus and into the babys heart, and a balloon catheter used to create a hole between the left and right atria. This reduced the pressures in the pulmonary circulation and hence limited the damage to the lungs; but the tissues of a growing foetus have a remarkable ability to repair themselves, and the artificially created hole would often heal within a few weeks. Cardiologists needed to find a way of keeping it open until birth, when surgeons would be able to perform a more comprehensive repair.

In September 2005 a couple from Virginia, Angela and Jay VanDerwerken, visited their local hospital for a routine antenatal scan. They were devastated to learn that their unborn child had HLHS, and the prognosis was poor. The ultrasound pictures revealed an intact septum, making it likely that even before birth her lungs would be damaged beyond repair. They were told that they could either terminate the pregnancy or accept that their daughter would have to undergo open-heart surgery within hours of her birth, with only a 20% chance that she would survive.

Devastated, the VanDerwerkens returned home, where Angela researched the condition online. Although few hospitals offered any treatment for HLHS, she found several references to the Boston foetal cardiac intervention programme, the team of doctors that had pioneered the use of the balloon catheter during pregnancy.

They arranged an appointment with Wayne Tworetzky, the director of foetal cardiology at Boston Childrens Hospital, who performed a scan and confirmed that their unborn childs condition was treatable. A greying, softly spoken South African, Tworetzky explained that his team had recently developed a new procedure, but that it had never been tested on a patient. It would mean not just making a hole in the septum, but also inserting a device to prevent it from closing. The VanDerwerkens had few qualms about accepting the opportunity: the alternatives gave their daughter a negligible chance of life.

The procedure took place at Brigham and Womens Hospital in Boston on 7 November 2005, 30 weeks into the pregnancy, in a crowded operating theatre. Sixteen doctors, with a range of specialisms, took part: cardiologists, surgeons, and four anaesthetists two to look after the mother, two for her unborn child. Mother and child needed to be completely immobilised during a delicate procedure lasting several hours, so both were given a general anaesthetic. The team watched on the screen of an ultrasound scanner as a thin needle was guided through the wall of the uterus, then the foetuss chest and finally into her heart an object the size of a grape.

A guidewire was placed in the cardiac chambers, then a tiny balloon catheter was inserted and used to create an opening in the atrial septum. This had all been done before; but now the cardiologists added a refinement. The balloon was withdrawn, then returned to the heart, this time loaded with a 2.5 millimetre stent that was set in the opening between the left and right atria. There was a charged silence as the balloon was inflated to expand the stent; then, as the team saw on the monitor that blood was flowing freely through the aperture, the room erupted in cheers.

Grace VanDerwerken was born in early January after a normal labour, and shortly afterwards underwent open-heart surgery. After a fortnight she was allowed home, her healthy pink complexion proving that the interventions had succeeded in producing a functional circulation.

But just when she seemed to be out of danger, Grace died suddenly at the age of 36 days not as a consequence of the surgery, but from a rare arrhythmia, a complication of HLHS that occurs in just 5%. This was the cruellest luck, when she had seemingly overcome the grim odds against her. Her death was a tragic loss, but her parents courage had brought about a new era in foetal surgery.

Much of the most exciting contemporary research focuses on the greatest, most fundamental cardiac question of all: what can the surgeon do about the failing heart? Half a century after Christiaan Barnard performed the first human heart transplant, transplantation remains the gold standard of care for patients in irreversible heart failure once drugs have ceased to be effective. It is an excellent operation, too, with patients surviving an average of 15 years. But it will never be the panacea that many predicted, because there just arent enough donor hearts to go round.

With too few organs available, surgeons have had to think laterally. As a result, a new generation of artificial hearts is now in development. Several companies are now working on artificial hearts with tiny rotary electrical motors. In addition to being much smaller and more efficient than pneumatic pumps, these devices are far more durable, since the rotors that impel the blood are suspended magnetically and are not subject to the wear and tear caused by friction. Animal trials have shown promising results, but, as yet, none of these have been implanted in a patient.

Another type of total artificial heart, as such devices are known, has, however, recently been tested in humans. Alain Carpentier, an eminent French surgeon still active in his ninth decade, has collaborated with engineers from the French aeronautical firm Airbus to design a pulsatile, hydraulically powered device whose unique feature is the use of bioprosthetic materials both organic and synthetic matter. Unlike earlier artificial hearts, its design mimics the shape of the natural organ; the internal surfaces are lined with preserved bovine pericardial tissue, a biological surface far kinder to the red blood cells than the polymers previously used. Carpentiers artificial heart was first implanted in December 2013. Although the first four patients have since died two following component failures the results were encouraging, and a larger clinical trial is now under way.

One drawback to the artificial heart still leads many surgeons to dismiss the entire concept out of hand: the price tag. These high-precision devices cost in excess of 100,000 each, and no healthcare service in the world, publicly or privately funded, could afford to provide them to everybody in need of one. And there is one still more tantalising notion: that we will one day be able to engineer spare parts for the heart, or even an entire organ, in the laboratory.

In the 1980s, surgeons began to fabricate artificial skin for burns patients, seeding sheets of collagen or polymer with specialised cells in the hope that they would multiply and form a skin-like protective layer. But researchers had loftier ambitions, and a new field tissue engineering began to emerge.

High on the list of priorities for tissue engineers was the creation of artificial blood vessels, which would have applications across the full range of surgical specialisms. In 1999 surgeons in Tokyo performed a remarkable operation in which they gave a four-year-old girl a new artery grown from cells taken from elsewhere in her body. She had been born with a rare congenital defect which had completely obliterated the right branch of her pulmonary artery, the vessel conveying blood to the right lung. A short section of vein was excised from her leg, and cells from its inside wall were removed in the laboratory. They were then left to multiply in a bioreactor, a vessel that bathed them in a warm nutrient broth, simulating conditions inside the body.

After eight weeks, they had increased in number to more than 12m, and were used to seed the inside of a polymer tube which functioned as a scaffold for the new vessel. The tissue was allowed to continue growing for 10 days, and then the graft was transplanted. Two months later the polymer scaffold around the tissue, designed to break down inside the body, had completely dissolved, leaving only new tissue that would it was hoped grow with the patient.

At the turn of the millennium, a new world of possibility opened up when researchers gained a powerful new tool: stem cell technology. Stem cells are not specialised to one function but have the potential to develop into many different tissue types. One type of stem cell is found in growing embryos, and another in parts of the adult body, including the bone marrow (where they generate the cells of the blood and immune system) and skin. In 1998 James Thomson, a biologist at the University of Wisconsin, succeeded in isolating stem cells from human embryos and growing them in the laboratory.

But an arguably even more important breakthrough came nine years later, when Shinya Yamanaka, a researcher at Kyoto University, showed that it was possible to genetically reprogram skin cells and convert them into stem cells. The implications were enormous. In theory, it would now be possible to harvest mature, specialised cells from a patient, reprogram them as stem cells, then choose which type of tissue they would become.

Sanjay Sinha, a cardiologist at the University of Cambridge, is attempting to grow a patch of artificial myocardium (heart muscle tissue) in the laboratory for later implantation in the operating theatre. His technique starts with undifferentiated stem cells, which are then encouraged to develop into several types of specialised cell. These are then seeded on to a scaffold made from collagen, a tough protein found in connective tissue. The presence of several different cell types means that when they have had time to proliferate, the new tissue will develop its own blood supply.

Clinical trials are still some years away, but Sinha hopes that one day it will be possible to repair a damaged heart by sewing one of these patches over areas of muscle scarred by a heart attack.

Using advanced tissue-engineering techniques, researchers have already succeeded in creating replacement valves from the patients own tissue. This can be done by harvesting cells from elsewhere in the body (usually the blood vessels) and breeding them in a bioreactor, before seeding them on to a biodegradable polymer scaffold designed in the shape of a valve. Once the cells are in place they are allowed to proliferate before implantation, after which the scaffold melts away, leaving nothing but new tissue. The one major disadvantage of this approach is that each valve has to be tailor-made for a specific patient, a process that takes weeks. In the last couple of years, a group in Berlin has refined the process by tissue-engineering a valve and then stripping it of cellular material, leaving behind just the extracellular matrix the structure that holds the cells in position.

The end result is therefore not quite a valve, but a skeleton on which the body lays down new tissue. Valves manufactured in this way can be implanted, via catheter, in anybody; moreover, unlike conventional prosthetic devices, if the recipient is a child the new valve should grow with them.

If it is possible to tissue-engineer a valve, then why not an entire heart? For many researchers this has come to be the ultimate prize, and the idea is not necessarily as fanciful as it first appears.

In 2008, a team led by Doris Taylor, a scientist at the University of Minnesota, announced the creation of the worlds first bioartificial heart composed of both living and manufactured parts. They began by pumping detergents through hearts excised from rats. This removed all the cellular tissue from them, leaving a ghostly heart-shaped skeleton of extracellular matrix and connective fibre, which was used as a scaffold onto which cardiac or blood-vessel cells were seeded. The organ was then cultured in a bioreactor to encourage cell multiplication, with blood constantly perfused through the coronary arteries. After four days, it was possible to see the new tissue contracting, and after a week the heart was even capable of pumping blood though only 2% of its normal volume.

This was a brilliant achievement, but scaling the procedure up to generate a human-sized heart is made far more difficult by the much greater number of cells required. Surgeons in Heidelberg have since applied similar techniques to generate a human-sized cardiac scaffold covered in living tissue. The original heart came from a pig, and after it had been decellularised it was populated with human vascular cells and cardiac cells harvested from a newborn rat. After 10 days the walls of the organ had become lined with new myocardium which even showed signs of electrical activity. As a proof of concept, the experiment was a success, though after three weeks of culture the organ could neither contract nor pump blood.

Growing tissues and organs in a bioreactor is a laborious business, but recent improvements in 3D printing offer the tantalising possibility of manufacturing a new heart rapidly and to order. 3D printers work by breaking down a three-dimensional object into a series of thin, two-dimensional slices, which are laid down one on top of another. The technology has already been employed to manufacture complex engineering components out of metal or plastic, but it is now being used to generate tissues in the laboratory. To make an aortic valve, researchers at Cornell University took a pigs valve and X-rayed it in a high-resolution CT scanner. This gave them a precise map of its internal structure which could be used as a template. Using the data from the scan, the printer extruded thin jets of a hydrogel, a water-absorbent polymer that mimics natural tissue, gradually building up a duplicate of the pig valve layer by layer. This scaffold could then be seeded with living cells and incubated in the normal way.

Pushing the technology further, Adam Feinberg, a materials scientist at Carnegie Mellon University in Pittsburgh, recently succeeded in fabricating the first anatomically accurate 3D-printed heart. This facsimile was made of hydrogel and contained no tissue, but it did show a remarkable fidelity to the original organ. Since then, Feinberg has used natural proteins such as fibrin and collagen to 3D-print hearts. For many researchers in this field, a fully tissue-engineered heart is the ultimate prize.

We are left with several competing visions of the future. Within a few decades it is possible that we will be breeding transgenic pigs in vast sterile farms and harvesting their hearts to implant in sick patients. Or that new organs will be 3D-printed to order in factories, before being dispatched in drones to wherever they are needed. Or maybe an unexpected breakthrough in energy technology will make it possible to develop a fully implantable, permanent mechanical heart.

Whatever the future holds, it is worth reflecting on how much has been achieved in so little time. Speaking in 1902, six years after Ludwig Rehn became the first person to perform cardiac surgery, Harry Sherman remarked that the road to the heart is only two or three centimetres in a direct line, but it has taken surgery nearly 2,400 years to travel it. Overcoming centuries of cultural and medical prejudice required a degree of courage and vision still difficult to appreciate today. Even after that first step had been taken, another 50 years elapsed before surgeons began to make any real progress. Then, in a dizzying period of three decades, they learned how to open the heart, repair and even replace it. In most fields, an era of such fundamental discoveries happens only once if at all and it is unlikely that cardiac surgeons will ever again captivate the world as Christiaan Barnard and his colleagues did in 1967. But the history of heart surgery is littered with breakthroughs nobody saw coming, and as long as there are surgeons of talent and imagination, and a determination to do better for their patients, there is every chance that they will continue to surprise us.

Main photograph: Getty Images

This is an adapted extract from The Matter of the Heart by Thomas Morris, published by the Bodley Head

Follow the Long Read on Twitter at @gdnlongread, or sign up to the long read weekly email here.

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Robot hearts: medicine's new frontier - The Guardian

Cardiac Stem Cells Comments Off on Robot hearts: medicine’s new frontier – The Guardian | May 23rd, 2017

Rio Sugimura

Researchers made these blood stem cells and progenitor cells from human induced pluripotent stem cells.

After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today in Nature1, 2, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature1. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells2.

For many years, people have figured out parts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells into induced pluripotent stem (iPS) cells, which are capable of producing many other cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factors genes that control other genes into the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full life more than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, Bhatia says. I hoped the critics were wrong, and now I know they were.

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Lab-grown blood stem cells produced at last - Nature.com

Skin Stem Cells Comments Off on Lab-grown blood stem cells produced at last – Nature.com | May 22nd, 2017

Exercise can burn the fat found within bone marrow, according to new research. The work, conducted with mice, offers evidence that this process improves bone quality and increases the amount of bone in a matter of weeks.

The study also suggests obese individuals who often have worse bone quality may derive even greater bone health benefits from exercising than their leaner counterparts. Lead author Maya Styner, a physician and assistant professor of endocrinology and metabolism at the University of North Carolina at Chapel Hill, said:

One of the main clinical implications of this research is that exercise is not just good, but amazing for bone health. In just a very short period of time, we saw that running was building bone significantly in mice.

Although research in mice is not directly translatable to the human condition, the kinds of stem cells that produce bone and fat in mice are the same kind as those that produce bone and fat in humans.

In addition to its implications for obesity and bone health, Styner says the research also could help illuminate some of the factors behind bone degradation associated with conditions like diabetes, arthritis, anorexia, and the use of steroid medications.

I see a lot of patients with poor bone health, and I always talk to them about what a dramatic effect exercise can have on bones, regardless of what the cause of their bone condition is, says Styner. With obesity, it seems that you get even more bone formation from exercise. Our studies of bone biomechanics show that the quality and the strength of the bone is significantly increased with exercise and even more so in the obese exercisers.

Bone marrow coordinates the formation of bone and cartilage while simultaneously churning out blood cells, immune cells, and cancerous cells.

Marrow also produces fat, but the physiological role of bone marrow fat in the body and even whether it is beneficial or harmful for ones health has remained somewhat mysterious.

Generally, marrow fat has been thought to comprise a special fat reserve that is not used to fuel energy during exercise in the same way other fat stores are used throughout the body during exercise. The new study offers evidence to the contrary.

Styners work also offers fundamental insights on how marrow fat forms and the impact it has on bone health. Previous studies have suggested that a higher amount of marrow fat increases the risk of fractures and other problems.

Theres been intense interest in marrow fat because its highly associated with states of low bone density, but scientists still havent understood its physiologic purpose, says Styner. We know that exercise has a profound effect on fat elsewhere in the body, and we wanted to use exercise as a tool to understand the fat in the marrow.

The research leaves a few lingering mysteries. A big one is figuring out the exact relationship between burning marrow fat and building better bone.

It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone. Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates these stem cells to churn out more bone cells and less fat cells.

More research will be needed to clarify all this.

What we can say is theres a lot of evidence suggesting that marrow fat is being used as fuel to make more bone, rather than there being an increase in the diversion of stem cells into bone, says Styner.

The National Institutes of Health Funded this research.

Styner, M., Pagnotti, G. M., McGrath, C., Wu, X., Sen, B., Uzer, G., Xie, Z., Zong, X., Styner, M. A., Rubin, C. T. and Rubin, J. (2017) Exercise Decreases Marrow Adipose Tissue Through -Oxidation in Obese Running Mice J Bone Miner Res. doi:10.1002/jbmr.3159

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Exercise Decreases Fat In Bone Marrow Through -Oxidation - ReliaWire

Bone Marrow Stem Cells Comments Off on Exercise Decreases Fat In Bone Marrow Through -Oxidation – ReliaWire | May 20th, 2017

Science Daily

Another reason to exercise: Burning bone fat a key to better bone health Science Daily It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone. Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates ... and more »

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Another reason to exercise: Burning bone fat a key to better bone health - Science Daily

Bone Marrow Stem Cells Comments Off on Another reason to exercise: Burning bone fat a key to better bone health – Science Daily | May 19th, 2017

Scientists have healed severe bone fractures in pigs by blasting tiny bubbles with ultrasound in the animals bones. The technique encourages the pigs bodies to regenerate themselves, and could one day be used to help humans especially the elderly heal dangerous bone injuries.

Broken bones are common: you wrap an arm or wrist in a cast and the bone eventually heals on its own. But sometimes, people have nonunion fractures, meaning bones fail to produce new bone tissue and dont heal properly. There are about 100,000 cases of this in the United States every year. One solution is bone grafts, or bone transplants using donated marrow, but this procedure is invasive and there is a risk that the body will reject the marrow. Another solution is to use viruses to deliver bone morphogenetic proteins (BMPs) that encourage the bodys own stem cells to create more bone marrow. But using a virus can have negative side effects like inflammation.

In a study published today in Science Translational Medicine, scientists healed a 0.4-inch fracture in pigs in eight weeks without invasive surgery. Going from something invasive to something like this that potentially could be an outpatient procedure has been the holy grail in orthopedics, says Edward Schwarz, director of the University of Rochesters Center for Musculoskeletal Research, who was not involved with the study. He adds that, though these nonunion fractures arent the most common health problem, theyre a serious one. People are shocked when I tell them that the life expectancy with a nonunion fracture is shorter than with pancreatic cancer, he says. Were like horses. If we cant get up and walk again, then were done.

In the study, the researchers first caused a 0.4-inch fracture in the shins of 18 minipigs. Then, they inserted a biodegradable scaffolds into the broken shins, says co-author Gadi Pelled, a professor of surgery at Cedars-Sinai Medical Center. The scaffold helped support bone stem cells in the area. The scientists let the stem cells migrate and populate over the scaffold for two weeks but that wast enough. The stem cells had to be triggered to actually heal the injury. So the scientists injected microbubbles mixed with bone morphogenetic proteins. Immediately after the injection, they applied ultrasound, which stimulated the BMPs to enter into the stem cells and activate them.

The stem cells then turned into bone cells and healed the fracture after eight weeks. This method doesnt have the side effects associated with using viruses, and the fact that it uses the bodys own stem cells means theres no risk of rejection, says co-author Zulma Gazit, also at Cedars-Sinai. This ultrasound and microbubbles combo has already been approved by the Food and Drug Administration and is often used in radiology, so the new technique could be readily approved for use in humans.

Next, says Pelled, the team is studying whether the same technology can also work with tissues like ligaments; they gathering more comprehensive information. Before we move forward into humans, we need to determine that this technology is safe, says Pelled. Theyre hopeful that a clinical trial is on the way.

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Blasting tiny bubbles at broken pig bones makes them heal on their own - The Verge

Bone Marrow Stem Cells Comments Off on Blasting tiny bubbles at broken pig bones makes them heal on their own – The Verge | May 18th, 2017

A team of scientists has successfully repaired the broken bones of lab animals without invasive surgery, by using microbubbles and ultrasound to stimulate the growth of stem cells.

In a study published in the journal Science Translational Medicine on Wednesday, Maxim Bez and a team of Cedars Sinai-led scientists were able to facilitate the natural growth of stem cells to create more bone marrow in broken bones that cannot heal on their own, known as nonunion fractures.

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While certain bone injuries only require a few weeks in a cast to heal, more severe injuries can cause large gaps between the edges of a fracture that cannot be healed without invasive surgery or bone grafting.

There are currently two methods for bone grafting, either using autografts that transfer bone marrow from a different part of the patients own body, or allografts that use donated bone marrow from another patient. Artificial transplants are often rejected by the body, making another bone graft necessary.

There are more than 2 million bone grafting procedures performed around the world each year, with roughly 100,000 cases in the US alone.

Nonunion bone fractures can cause great damage to the body, leaving patients crippled or with other severe complications.

In a first of its kind study, Bez and his team developed an alternative that uses microbubbles and ultrasound to facilitate the bodys natural stem-cell growth.

"This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal's own stem cells can effectively be used to treat nonhealing bone fractures," said Gadi Pelled, assistant professor of surgery at Cedars-Sinai and co-author of the study, according to Medical XPress. "It addresses a major orthopedic unmet need and offers new possibilities for clinical translation."

In the study, Bez and his team first created severe bone fractures the tibiae bones of large pigs. Then, they inserted a biodegradable collagen scaffold in the fracture, which supported stem cell growth. Two weeks later, after the stem cells grew around the scaffold, the scientists injected microbubbles containing growth-promoting genes. Finally, they used an ultrasound pulse, which causes the stems cells to become bone cells, healing the fracture.

The technique was able to completely heal nonunion fractures in eight weeks. Bez and his team found their method healed bones to the point that they were just as strong as those treated with bone grafts.

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The technique is minimally invasive and does not have the side effects associated with bone grafts. If the method is found to be safe for humans, it would provide patients with an alternative to replace bone grafting.

Bez and his team say that their method could potentially be used in tissue engineering applications in the future.

"We are just at the beginning of a revolution in orthopedics," said Dan Gazit, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-author of the study, according to Medical XPress. "We're combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine."

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'Future of medicine': Broken pig bones healed using tiny bubbles & ultrasound - RT

Bone Marrow Stem Cells Comments Off on ‘Future of medicine’: Broken pig bones healed using tiny bubbles & ultrasound – RT | May 18th, 2017

International Stem Cell Corporation Announces Operating Results for the Quarter ended March 31, 2017 P&T Community ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin ... and more »

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International Stem Cell Corporation Announces Operating Results for the Quarter ended March 31, 2017 - P&T Community

Skin Stem Cells Comments Off on International Stem Cell Corporation Announces Operating Results for the Quarter ended March 31, 2017 – P&T Community | May 18th, 2017