DAVID GRANOVSKY

Posts Tagged ‘transplant’

ULTRASOUND GOES INSIDE LIVE CELLS

In ALL ARTICLES, SCIENCE & STEM CELLS on February 17, 2017 at 9:06 am

Researchers at The University of Nottingham have developed a break-through technique that uses sound rather than light to see inside live cells…like ultrasound on the body, ultrasound in the cells causes no damage and requires no toxic chemicals to work. Because of this we can see inside cells that one day might be put back into the body, for instance as stem-cell transplants

fat-cells1

Researchers at The University of Nottingham have developed a break-through technique that uses sound rather than light to see inside live cells, with potential application in stem-cell transplants and cancer diagnosis.

The new nanoscale ultrasound technique uses shorter-than-optical wavelengths of sound and could even rival the optical super-resolution techniques which won the 2014 Nobel Prize for Chemistry.

This new kind of sub-optical phonon (sound) imaging provides invaluable information about the structure, mechanical properties and behaviour of individual living cells at a scale not achieved before.

Researchers from the Optics and Photonics group in the Faculty of Engineering, University of Nottingham, are behind the discovery, which is published in the paper ‘High resolution 3D imaging of living cells with sub-optical wavelength phonons’ in the journal, Scientific Reports.

“People are most familiar with ultrasound as a way of looking inside the body — in the simplest terms we’ve engineered it to the point where it can look inside an individual cell. Nottingham is currently the only place in the world with this capability,” said Professor Matt Clark, who contributed to the study.

In conventional optical microscopy, which uses light (photons), the size of the smallest object you can see (or the resolution) is limited by the wavelength.

For biological specimens, the wavelength cannot go smaller than that of blue light because the energy carried on photons of light in the ultraviolet (and shorter wavelengths) is so high it can destroy the bonds that hold biological molecules together damaging the cells.

Optical super-resolution imaging also has distinct limitations in biological studies. This is because the fluorescent dyes it uses are often toxic and it requires huge amounts of light and time to observe and reconstruct an image which is damaging to cells.

Unlike light, sound does not have a high-energy payload. This has enabled the Nottingham researchers to use smaller wavelengths and see smaller things and get to higher resolutions without damaging the cell biology.

“A great thing is that, like ultrasound on the body, ultrasound in the cells causes no damage and requires no toxic chemicals to work. Because of this we can see inside cells that one day might be put back into the body, for instance as stem-cell transplants,” adds Professor Clark.

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More information is available from Professor Matt Clark in the Faculty of Engineering, University of Nottingham on +44 (0)115 951 5536, matt.clark@nottingham.ac.uk; or Emma Lowry, Media Relations Manager, on +44 (0)115 846 7156, emma.lowry@nottingham.ac.uk

Our academics can now be interviewed for broadcast via our Media Hub, which offers a Globelynx fixed camera and ISDN line facilities at University Park campus. For further information please contact a member of the Communications team on +44 (0)115 951 5798, email mediahub@nottingham.ac.uk or see the Globelynx website for how to register for this service.

About The University of Nottingham: The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with a “distinct” approach to internationalisation, which rests on those full-scale campuses in China and Malaysia, as well as a large presence in its home city.’ (Times Good University Guide 2016). It is also one of the most popular universities in the UK among graduate employers and winner of both ‘University of the Year for Graduate Employment’, according to the 2017 The Times and The Sunday Times Good University Guide and ‘Outstanding Support for Early Career Researchers’ at the Times Higher Education Awards 2015. It is ranked in the world’s top 75 by the QS World University Rankings 2015/16. More than 97 per cent of research at The University of Nottingham is recognised internationally and it is 8th in the UK by research power according to the Research Excellence Framework 2014. It has been voted the world’s greenest campus for four years running, according to Greenmetrics Ranking of World Universities.

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INTER-SPECIES PANCREAS TRANSPLANT REVERSES DIABETES

In HEALTH AND WELLNESS, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on February 8, 2017 at 12:33 pm

Color Rat Laboratory Cage Mammal Rat Rodent Pet

Let’s take a page out of what was not too long ago science fiction; which is now science-fact.

  • A pancreas was grown in a rat,
  • the organ was transplanted into a mouse,
  • the mouse was given immunosuppressive therapy to prevent rejection,
  • the diabetic mice were able to normalize their blood glucose levels for over a year.

This illustrates the long proven regenerative capacity of stem cells and the recent advancements scientists have made with anti-rejection protocols…And of course, the cool inter-species transplant of rat to mouse.

Rat-grown mouse pancreases help reverse diabetes in mice

Growing organs from one species in the body of another may one day relieve transplant shortages. Now researchers show that islets from rat-grown mouse pancreases can reverse disease when transplanted into diabetic mice.

White rat with black patches

A rat in which researchers were able to grow a mouse pancreas. Islets from the pancreases were transplanted into mice with diabetes. The transplants helped control the mice’s blood sugar levels.
Courtesy of the Nakauchi lab

 Mouse pancreases grown in rats generate functional, insulin-producing cells that can reverse diabetes when transplanted into mice with the disease, according to researchers at the Stanford University School of Medicine and the Institute of Medical Science at the University of Tokyo.

The recipient animals required only days of immunosuppressive therapy to prevent rejection of the genetically matched organ rather than lifelong treatment.

The success of the interspecies transplantation suggests that a similar technique could one day be used to generate matched, transplantable human organs in large animals like pigs and sheep.

To conduct the work, the researchers implanted mouse pluripotent stem cells, which can become any cell in the body, into early rat embryos. The rats had been genetically engineered to be unable to develop their own pancreas and were thus forced to rely on the mouse cells for the development of the organ.

Once the rats were born and grown, the researchers transplanted the insulin-producing cells, which cluster together in groups called islets, from the rat-grown pancreases into mice genetically matched to the stem cells that formed the pancreas. These mice had been given a drug to cause them to develop diabetes.

“We found that the diabetic mice were able to normalize their blood glucose levels for over a year after the transplantation of as few as 100 of these islets,” said Hiromitsu Nakauchi, MD, PhD, a professor of genetics at Stanford. “Furthermore, the recipient animals only needed treatment with immunosuppressive drugs for five days after transplantation, rather than the ongoing immunosuppression that would be needed for unmatched organs.”

Nakauchi, who is a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, is the senior author of a paper describing the findings, which was published online Jan. 25 in Nature. Tomoyuki Yamaguchi, PhD, an associate professor of stem cell therapy, and researcher Hideyuki Sato, both from the University of Tokyo, share lead authorship of the paper.

Hiro Nakauchi

Although much research remains to be done, scientist Hiromitsu Nakauchi and his colleagues believe their work with rodents shows that a similar technique could one day be used to generate matched, transplantable human organs in large animals like pigs and sheep.
Wing Hon Films

Organs in short supply

About 76,000 people in the United States are currently waiting for an organ transplant, but organs are in short supply. Generating genetically matched human organs in large animals could relieve the shortage and release transplant recipients from the need for lifelong immunosuppression, the researchers say.

People suffering from diabetes could also benefit from this approach. Diabetes is a life-threating metabolic disease in which a person or animal is unable to either make or respond appropriately to insulin, which is a hormone that allows the body to regulate its blood sugar levels in response to meals or fasting. The disease affects hundreds of millions of people worldwide and is increasing in prevalence. The transplantation of functional islets from healthy pancreases has been shown to be a potentially viable option to treat diabetes in humans, as long as rejection can be avoided.

The researchers’ current findings come on the heels of a previous study in which they grew rat pancreases in mice. Although the organs appeared functional, they were the size of a normal mouse pancreas rather than a larger rat pancreas. As a result, there were not enough functional islets in the smaller organs to successfully reverse diabetes in rats.

Mouse pancreases grown in rats

In the current study, the researchers swapped the animals’ roles, growing mouse pancreases in rats engineered to lack the organ. The pancreases were able to successfully regulate the rats’ blood sugar levels, indicating they were functioning normally. Rejection of the mouse pancreases by the rats’ immune systems was uncommon because the mouse cells were injected into the rat embryo prior to the development of immune tolerance, which is a period during development when the immune system is trained to recognize its own tissues as “self.” Most of these mouse-derived organs grew to the size expected for a rat pancreas, rendering enough individual islets for transplantation

Next, the researchers transplanted 100 islets from the rat-grown pancreases back into mice with diabetes. Subsequently, these mice were able to successfully control their blood sugar levels for over 370 days, the researchers found.

Because the transplanted islets contained some contaminating rat cells, the researchers treated each recipient mouse with immunosuppressive drugs for five days after transplant. After this time, however, the immunosuppression was stopped.

After about 10 months, the researchers removed the islets from a subset of the mice for inspection.

“We examined them closely for the presence of any rat cells, but we found that the mouse’s immune system had eliminated them,” said Nakauchi. “This is very promising for our hope to transplant human organs grown in animals because it suggests that any contaminating animal cells could be eliminated by the patient’s immune system after transplant.”

Importantly, the researchers also did not see any signs of tumor formation or other abnormalities caused by the pluripotent mouse stem cells that formed the islets. Tumor formation is often a concern when pluripotent stem cells are used in an animal due to the cells’ remarkable developmental plasticity. The researchers believe the lack of any signs of cancer is likely due to the fact that the mouse pluripotent stem cells were guided to generate a pancreas within the developing rat embryo, rather than coaxed to develop into islet cells in the laboratory. The researchers are working on similar animal-to-animal experiments to generate kidneys, livers and lungs.

Although the findings provide proof-of-principle for future work, much research remains to be done. Ethical considerations are also important when human stem cells are transplanted into animal embryos, the researchers acknowledge.

The research was funded by the Japan Science and Technology Agency, the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, a KAKENHI grant, the Japan Insulin Dependent Diabetes Mellitus Network and the California Institute for Regenerative Medicine.

Stanford’s Department of Genetics also supported the work.

NEW HOPE FOR SOLDIERS DISFIGURED IN WAR

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on August 8, 2014 at 11:08 am
face-of-hope

Stem cells as part of every treatment protocol
What if stem cells could be used in conjunction with other treatments and in doing so, make the impossible, possible?  Well…they are starting to.  “Army surgeon Robert Hale is leading the charge to make facial reconstruction medicine ready for the wounds of 21st-century war.”

A great deal of scientific and anecdotal evidence substantiate that stem cells are a seemingly limitless potential cure-all and one of the greatest medical advancements known to man.  While the safety and efficacy of stem cell therapy when utilized as an isolated therapy is virtually undeniable, the full extent of stem cells’ healing potential is even more awe-inspiring.  Stem cells can potentially become complements to thousands of other treatments due to:

  • their regenerative capabilities
  • their flexibility
  • the fact that they are part of the body’s natural healing system

Stem cells have been used successfully to reduce symptoms and alleviate the suffering of hundreds of conditions previously believed to be incurable and they are often best utilized in isolation.  In fact, many stem cell doctors believe they work best when manipulated or modified as little as possible.  On the other hand, they have shown great success when used with other treatment protocols.  The oldest example is the 6 decades of stem cell use in the form of Bone Marrow Transplants and in coordination with chemo to mitigate Leukemia, Hodgkin’s and Non-Hodgkin’s Lymphomas and other blood cancers.  When used with an “other” effective treatment, the result is often greater than the sum of the parts as the stem cells contribute to the healing potential of the “other” protocol.

In the article below, Army surgeon Robert Hale combines multiple techniques and protocols with stem cell therapy with a patient whose injuries were so severe, they were arranging organ donation.  This “protocol stacking” of cutting edge facial reconstruction, cutting edge stem cell therapy, superclavicle flap grafting from 1917 and other techniques allowed him to accomplish what was previously impossible.  .

Used alone, stem cells have a proven history of success as the “this changes everything” element in regenerative medicine and modern healing.

Used in conjunction with other established protocols or with new technologies, stem cells may very well change everything we have come to expect from modern medicine.

By the way, we saw this coming 3 years ago in DAMN! SILENCE OF THE LAMBS MEETS STEM CELLS!

SILENCE OF THE LAMBS MEETS STEM CELLS and future transplant recipients win big!!  Remember in Silence of the Lambs, at the end of the movie, when Hannibal Lechter cuts off the guards face and then wears it out to escape?  It turns out, if he had some stem cells to go with that face transplant, he could have just kept on wearing it.  Surgical researchers did exactly that on four dogs and all 4 of the dogs tolerated the face transplants for over one year without immunosuppressive drugs after the first month.

New Hope for Soldiers Disfigured in War

Army surgeon Robert Hale is leading the charge to make facial reconstruction medicine ready for the wounds of 21st-century war.

Col. Robert Hale shows a prototype of a mask that would speed healing and help prevent infection in treatment of facial injuries in soldiers. The design and function of the biomask has evolved as Hale has worked with research teams at Fort Sam Houston in San Antonio…

http://discovermagazine.com/2014/sept/11-face-of-hope

NOW YOU DON’T SEE IT- NOW YOU DO

In ALL ARTICLES, SCIENCE & STEM CELLS on July 10, 2014 at 9:39 am

Now You Don’t See it- Now You Do
Author: Sarah Hoffman

660_Mans_Eye.jpg

“Boston researchers have successfully regrown human corneal tissue – a feat that could potentially restore vision in the blind.

The achievement also marks one of the first times that scientists have constructed tissue using adult-derived human stem cells.-Researchers Regrow Corneas Using Adult Human Stem Cells’. FoxNews.com

Researchers recently made great strides in the field of regrowing human tissue– this time regrowing a human cornea using adult stem cells. This is an amazing feat. They discovered that not only is it possible to regrow a cornea using cells from the functioning eye of someone who is blind in only one eye, but they can also transplant cells from a donor and regrow that way. They tested all this on mice, but used human adult stem cells. This is pretty darn cool.

And why is this possible now? Well the original hold up was their inability to harvest a specific molecule called ABCB5, which is necessary when growing corneal tissue. These researchers discovered that a high concentration of these molecules can be found in the eyes limbus (basically the white part of your eye), which in hindsight makes perfect sense. Unfortunately these cells die when the eye goes blind, but people suffering from blindness have one good eye full of these little miracle-workers. And those with blindness in both eyes can receive a transplant, though they may need immune-suppression.

These leaves only one obvious question to be answered– do these mice see as mice see? Or do they now see as us humans do? Philosophical input is welcome…

GUT BACTERIA = STRONGER STEM CELL RESPONSE

In ALL ARTICLES, STEM CELLS IN THE NEWS on June 23, 2014 at 4:03 pm

Aliens or martians cartoon illustration

Gut Bacteria= Stronger Stem Cell Response

“The diversity of bacteria in the gastrointestinal tract of patients receiving stem cell transplants may be an important predictor of their post-transplant survival, researchers report. Researchers found a strong connection between post-transplant gut microbiota diversity and outcomes, observing overall survival rates of 36 percent, 60 percent, and 67 percent among the low, intermediate, and high diversity groups, respectively.” – ‘Gut bacteria predict survival after stem cell transplant, study shows.’ ScienceDaily

I always believed it, now there’s proof!
http://www.sciencedaily.com/releases/2014/06/140617112226.htm

WHY? Maybe because…
Stem cells are a natural healing system in the body that regenerate dead and damaged tissue and create new tissue– they require nutrients to do so. Gut bacteria helps digest food and derive nutrients for the entire body. More gut bacteria means a stronger immune system which means a greater ability to fight infection; more nutrients available for use as building blocks, to repair nutrients, etc. This results in increased potential benefits from stem cell therapy.

 

SHE WASN’T DEAD ENOUGH FOR STEM CELLS IN THE US

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on June 19, 2014 at 9:22 am

Finding no promising treatment programs in the United States, and nothing that would be covered by her health insurance, Cristy traveled to Istanbul, Turkey, in 2011 for a life-saving stem-cell transplant

WHY!

CRISTY SCT
University of Hawaii Professor, Stem Cell Transplant Surgery Survivor and author of “5 Steps To Being Your Own Patient Advocate” is taking her “5 Steps Movement” on the road in July….

Cristy Kessler, Ed.D., NBCT

With over 19 years of teaching experience, Dr. Cristy Kessler has been motivating audiences of all ages with her message of determination, survival, faith, and hope. Cristy has a natural ability for speaking to large groups of people of all ages and a style of speaking that helps them feel like they’re sitting in her living room.

Cristy Kessler has been a role model for countless students from 5th grade through university whose lives she has touched as a social studies teacher, coach, and associate professor in education at the University of Hawaii. This, in spite of a lifetime of pain and a constant battle with health issues throughout her life.

A three-sport standout in high school, Cristy coached both soccer and basketball, including a five-year stint as coach for TourneySport USA in Hawaii. She earned her doctorate in educational leadership and innovation in 2003, and as part of her commitment to being the best teacher and role model she could be, she achieved certification through the National Board for Professional Teaching Standards (NBPTS), even though this certification is generally recognized as a program for K-12 teachers. Rarely has a university professor sought (or achieved) this recognition, but Cristy did exactly that in 2005, even as she was recovering from cancer surgery. In her role as an associate professor at the university, she has guided scores of teachers through successful achievement of NBPTS certification.

Plagued by constant pain and fatigue, Cristy was finally diagnosed in 2006 with a constellation of auto-immune diseases: scleroderma, ankylosing spondylitis, and vasculitis, any one of which is ultimately fatal. Following years of treatment for the symptoms of these disorders, it became clear that the only way to save her life was to somehow tackle the diseases themselves, not just the symptoms. Finding no promising treatment programs in the United States, and nothing that would be covered by her health insurance, Cristy traveled to Istanbul, Turkey, in 2011 for a life-saving stem-cell transplant at Anadolu Hospital, an affiliate of Johns Hopkins University. Extensive fund-raising efforts by friends and family helped make this incredible journey a reality.

The transplant succeeded such that Cristy has a brand-new immune system and has resumed her work with university students and teachers. She continues to look for opportunities to inspire and encourage others through the story of her determination to live, even in the face of chronic pain and imminent death.

Dr. Kessler recently released a new book, “5 Steps To Being Your Own Patient Advocate” and is touring in July in support of the book.

Check out the current tour schedule at:
http://www.5stepstobeingyourownpatientadvocate.com

“My Health. My Body. My Voice….Learning To Live Tour” campaign:
https://www.indiegogo.com/projects/my-health-my-body-my-voice-learning-to-live-tour/x/3387656

You can read Cristy’s compelling story at:
http://www.cristykessler.com

Youtube Channel:
https://www.youtube.com/channel/UCoL–mQB2KXhcVkJXxMZwFg

KIDNEY BREAKTHROUGH: COMPLETE LAB GROWN ORGAN WORKS IN RATS

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on April 19, 2013 at 4:00 pm
A brand new rat kidney being built on the scaffold of an old one <i>(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)</i>

A brand new rat kidney being built on the scaffold of an old one

(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)

Kidney breakthrough: complete lab-grown organ works in rats

 

  • 18:00 14 April 2013 by Andy Coghlan

 

For the first time, complete lab-grown kidneys have been successfully transplanted into rats, filtering and discharging urine as a normal kidney would.

 

The breakthrough paves the way for human-scale versions, which could potentially provide an inexhaustible supply of organs, eliminating the need for recipients to wait for a matching donor kidney Movie Camera.

 

Similar techniques have already been applied successfully in people with simpler tissue, such as windpipes. But the kidney is by far the most complex organ successfully recreated.

 

“If this technology can be scaled to human-size grafts, patients suffering from renal failure, who are currently waiting for donor kidneys, could theoretically receive an organ grown on demand,” says Harald Ott, head of the team that developed the rat kidneys at the Massachusetts General Hospital in Boston.

 

“In an ideal world, such grafts could be produced from patient-derived cells, enabling us to overcome both donor organ shortages and the need for long-term immunosuppression drugs,” says Ott. Currently in the US alone, 18,000 transplants are carried out each year, but 100,000 Americans remain on waiting lists.

 

Strip and coat

 

To make the rat kidneys, Ott and his colleagues took kidneys from healthy “donor” rats and used a chemical solution to wash away the native cells, leaving behind the organ’s scaffold. Because this is made of collagen, a biologically inert material, there is no issue of the recipient’s body rejecting it.

 

Next, the team set about regrowing the “flesh” of the organ by coating the inner surfaces of the scaffold with new cells. In the case of humans, these would likely come from the recipient, so all the flesh would be their own.

 

The kidney was too complex to use the approach applied to the windpipe – in which its scaffold was coated by simply immersing it in a bath of the recipient’s cells.

 

Instead, the team placed the kidney scaffolds in glass chambers containing oxygen and nutrients, and attached tubes to the protruding ends of the renal artery, vein and ureter – through which urine normally exits the kidney. They recoated the insides of the blood vessels by flowing human stem cells through the tubes attached to the artery and vein. Through the ureter, they fed kidney cells from newborn rats, re-coating the labyrinthine tubules and ducts that make up the kidney’s urine filtration system.

 

It took many attempts to establish the precise pressures at which to feed the cells into the organ, as if it was growing in an embryonic rat. Remarkably, given the complexity of the kidney, the cells differentiated into exactly those required in the different compartments of the organ. “We found the correct cell types homed in to specific regions in the organ matrix,” says Ott.

 

The kidneys, which took about a fortnight to fully recoat, worked both in the lab and when transplanted into rats. They filtered out and discharged urine, although they did not sieve it as well as a natural kidney would. Ott is confident that the function can be improved by refining the technique.

 

Humans and pigs

 

The team is now attempting the same procedure using human kidneys, and also pig kidneys, which could be used to make scaffolds if there were a scarcity of human donors. The team has already successfully repopulated pig kidneys with human cells, but Ott says further studies are vital to guarantee that the pig components of the organ do not cause rejection when transplanted into humans.

 

The fact that heart valves and other “inert” tissues from pigs are already successfully used in humans without rejection suggests that this will not be a big problem.

 

Other researchers working in the field hailed the team’s success at recreating such a complex organ. “The researchers have taken a technique that most in the field thought would be impossible for complex organs such as the kidney, and have painstakingly developed a method to make it work,” says Jamie Davies at the University of Edinburgh, UK, who was part of a team that last year made some headway in their attempts to grow kidneys from scratch in the lab. “By showing that recellularisation is feasible even for complicated organs, their work will stimulate similar approaches to the engineering of other body systems.”

 

Journal reference: Nature Medicine, DOI: 10.1038/nm.3154

NEW STEM CELL TREATMENT STUDY FOCUSES ON PREVENTING SIGHT LOSS FROM DIABETICS

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on February 19, 2013 at 9:00 am

eye

Currently millions of diabetics worldwide are at risk of sight loss due to a condition called Diabetic Retinopathy. This is when high blood sugar causes the blood vessels in the eye to become blocked or to leak. Failed blood flow harms the retina and leads to vision impairment and if left untreated can lead to blindness.  Scientists at Queen’s University Belfast are hoping to develop a novel approach that could save the sight of millions of diabetes sufferers using adult stem cells.

The novel REDDSTAR study (Repair of Diabetic Damage by Stromal Cell Administration) involving researchers from Queen’s Centre for Vision and Vascular Science, will see them isolating stem cells from donors, expanding them in a laboratory setting and re-delivering them to a patient where they help to repair the blood vessels in the eye. This is especially relevant to patients with diabetes were the vessels of the retina become damaged.

At present there are very few treatments available to control the progression of diabetic complications. There are no treatments which will improve glucose levels and simultaneously treat the diabetic complication.  The research is being carried out with NUI Galway and brings together experts from Northern Ireland, Ireland, Germany, the Netherlands, Denmark, Portugal and the US.

Professor Alan Stitt, Director of the Centre for Vision and Vascular Science in Queen’s and lead scientist for the project said: “The Queen’s component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes. The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.

“Currently available treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages of the disease, carry many side effects and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy.”

“This new research project is one of several regenerative medicine approaches ongoing in the centre. The approach is quite simple: we plan to isolate a very defined population of stem cells and then deliver them to sites in the body that have been damaged by diabetes. In the case of some patients with diabetes, they may gain enormous benefit from stem cell-mediated repair of damaged blood vessels in their retina. This is the first step towards an exciting new therapy in an area where it is desperately needed.”

The project will develop ways to grow the bone-marrow-derived stem cells. They will be tested in several preclinical models of diabetic complications at centres in Belfast, Galway, Munich, Berlin and Porto before human trials take place in Denmark.

http://www.qub.ac.uk/research-centres/CentreforVisionandVascularScience/

HEARTS BEING REPAIRED THROUGH STEM CELLS

In ALL ARTICLES, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on February 5, 2013 at 9:00 am

xray_1834547c

Scientists Are Rebuilding Hearts With Stem Cells

Every two minutes someone in the UK has a heart attack.

Every six minutes, someone dies from heart failure.

During an attack, the heart remodels itself and dilates around the site of the injury to try to compensate, but these repairs are rarely effective. If the attack does not kill you, heart failure later frequently will.  “No matter what other clinical interventions are available, heart transplantation is the only genuine cure for this,” says Paul Riley, professor of regenerative medicine at Oxford University. “The problem is there is a dearth of heart donors.”  Transplants have their own problems – successful operations require patients to remain on toxic, immune-suppressing drugs for life and their subsequent life expectancies are not usually longer than 20 years.  The solution, emerging from the laboratories of several groups of scientists around the world, is to work out how to rebuild damaged hearts. Their weapons of choice are reprogrammed stem cells.

These researchers have rejected the more traditional path of cell therapy that you may have read about over the past decade of hope around stem cells – the idea that stem cells could be used to create batches of functioning tissue (heart or brain or whatever else) for transplant into the damaged part of the body.  Instead, these scientists are trying to understand what the chemical and genetic switches are that turn something into a heart cell or muscle cell. Using that information, they hope to program cells at will, and help the body make repairs.

It is an exciting time for a technology that no one thought possible a few years ago. In 2007, Shinya Yamanaka showed it was possible to turn adult skin cells into embryonic-like stem cells, called induced pluripotent stem cells (iPSCs), using just a few chemical factors.

His technique radically advanced stem cell biology, sweeping aside years of blockages due to the ethical objections about using stem cells from embryos. He won the Nobel prize in physiology or medicine for his work in October. Researchers have taken this a step further – directly turning one mature cell type to another without going through a stem cell phase.

At Oxford, Riley has spent almost a year setting up a lab to work out how to get heart muscle to repair itself. The idea is to expand the scope of the work that got Riley into the headlines last year after a high-profile paper published in the journal Nature in which he showed a means of repairing cells damaged during a heart attack in mice. That work involved in effect turning the clock back in a layer of cells on the outside of the heart, called the epicardium, making adult cells think they were embryos again and thereby restarting their ability to repair.

During the development of the embryo, the epicardium turns into the many types of cells seen in the heart and surrounding blood vessels. After the baby is born this layer of cells loses its ability to transform. By infusing the epicardium with the protein thymosin β4 (Tβ4), Riley’s team found the once-dormant layer of cells was able to produce new, functioning heart cells. Overall, the treatment led to a 25% improvement in the mouse heart’s ability to pump blood after a month compared with mice that had not received the treatment.

Riley says finding ways to replace damaged cells via transplantation, the dominant research idea for more than a decade, has faltered. Scientists have tried out a variety of adult stem cells – derived from areas such as bone marrow, muscle and fat – turned them into heart cells and transplanted them into animal models, which initially showed good results.  But those results could never be repeated in humans with the same degree of success. “In humans, moving into clinical trials, the actual benefit, from a meta-analysis just on bone-marrow-derived cells, is a meagre 3% improvement,” he says. “That’s barely detectable clinically and unfortunately isn’t going to make a vast amount of difference to your overall quality of life.”  The original impression from rodent studies was that the transplanted cells would become new muscle and contribute to improving damaged areas, but Riley says that idea has fallen out of favour. “All they do, if anything at all, is to secrete factors that will help the heart sustain the injury, rather than necessarily offer long-term regeneration.”

That is where the reprogrammers get going. Find the chemical factors that will make a cell (a skin cell, say, or a piece of scar tissue) think it is in the womb, so it switches certain genes on and others off and becomes a new heart cell, and you can avoid the large-scale transplant altogether. All you need is an infusion of the right drugs and resident cells will do all the required repair work.

The process requires an understanding of how an embryo develops and what cues nature uses to grow all the body’s cell types from just a sperm and an egg. This ability to regenerate does not quite stop at birth: injure a one-day-old mouse’s heart, for example, and it will completely regenerate. Injure it again after a week and the heart will scar. “Within seven days, it goes from completely repairable to the adult wound-healing default position,” says Riley. “We want to understand what happens during that window.”

Many scientists believe the secrets of how to regenerate tissue are linked with an understanding of how to reverse the ageing process. Saul Villeda, of the University of California, presented work at the recent annual meeting of the Society for Neuroscience in New Orleans where he showed that blood from young mice reversed some of the effects of ageing in older mice, improving learning and memory to a level comparable with much younger animals. Older mice had an increased number of stem cells in their brains and there was a 20% increase in connections between brain cells.

Though his work is yet to be published in a peer-reviewed journal, Villeda speculated the young blood was likely to be working in the older mice by increasing levels of chemical factors that tend to decline as animals get older. Bring these back, he says, and “all of a sudden you have all of these plasticity and learning and memory-related genes that are coming back”.

Prof Deepak Srivastava has already transformed scar-forming cardiac cells in mice into beating heart cells, inside living animals, using a set of chemical factors. His results were published last April in Nature.  “We’ve redeployed nature’s own toolkit in these cells to convert non-muscle cells that are in the heart into new muscle. More than half of the cells in the heart are not muscle [but] architectural cells called fibroblasts that are meant to support the muscle,” he says.

“We had the idea that if we could somehow fool those cells into thinking that they should become muscle, then we have a vast reservoir of cells that already exist within the organ that might be able to be called upon to regenerate the heart from within.”

He injected three chemical factors – called Gata4, Mef2c and Tbx5, collectively known as GMT – into the damaged region of a heart and, within a month, the non-beating cells that normally ended up becoming scar tissue had become functioning heart cells that had integrated with their neighbors.  “The factors get taken up by the fibroblasts and the non-muscle population of cells and they initiate a genome-wide switch of the program of the cells so that it now begins to activate thousands of muscle-specific genes and it turns off thousands of fibroblast genes.”

Srivastava’s direct reprogramming technique takes Yamanaka’s work further because it allows scientists to turn one type of cell into another without having to go through a stem cell phase in between, thus reducing the risk that any future therapy might induce cancer.  The method has been proven to work, so far only in Petri dishes, for blood, liver and brain cells. “Ultimately, as we learn enough about each cell type, it’s likely we might be able to make most cell types in the body with this direct reprogramming approach,” he says.

The tough task for all these scientists – from those working specifically on the heart such as Riley to those working more generally on all cell types such as Srivastava – is to identify and catalogue the thousands of chemical factors that are at work in the various stages of cell development, and that are the keys to the transformation of one cell into another.

“We’re trying to do the same experiments we did in the heart in the pig’s heart because it is very similar in size and physiology to human hearts. If it works there and it is safe, then we’d be ready for a human clinical trial,” says Srivastava.

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FDA APPROVED SCHWANN CELL TRANSPLANT

In ALL ARTICLES, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on January 29, 2013 at 9:00 am

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Doctors Perform First FDA Approved Schwann Cell Transplant in Patient with New Spinal Cord Injury

Doctors at The Miami Project to Cure Paralysis, a Center of Excellence at the University of Miami Miller School of Medicine, performed the first-ever Food and Drug Administration approved Schwann cell transplantation in a patient with a new spinal cord injury. The procedure, performed at the University of Miami/Jackson Memorial Medical Center, is a Phase 1 clinical trial designed to evaluate the safety and feasibility of transplanting the patient’s own Schwann cells.

“This historic clinical trial represents a giant step forward in a field of medicine where each tangible step has tremendous value. This trial, and these first patients in this trial specifically, are extremely important to our mission of curing paralysis,” said neurosurgeon Barth Green, M.D., Co-Founder and Chairman of The Miami Project, and Professor and Chair of Neurological Surgery. “The Miami Project team includes hundreds of scientists, clinicians, and technicians who have joined hands to make the ‘impossible possible,’ for which this trial is a key goal and dream now being realized. This achievement reaffirms that the tens of millions of dollars and the incalculable work hours were well invested in this first of a kind human Schwann cell project.”

Led by W. Dalton Dietrich, Ph.D., Scientific Director of The Miami Project and Professor of Neurological Surgery, Neurology and Cell Biology & Anatomy, the Schwann cell clinical trial team at The Miami Project is composed of a multidisciplinary group of basic science and clinical faculty members, scientific staff, and regulatory personnel focused on advancing the trial. The transplantation procedure was conducted by the Principal Investigators of the trial, Dr. Allan Levi, M.D., Ph.D., Professor of Neurological Surgery, Orthopedic, and Rehabilitation, and James Guest, M.D., Ph.D., Associate Professor of Neurological Surgery. The patient had a neurologically complete thoracic spinal injury and received the transplantation of autologous Schwann cells about four weeks post-injury. There have been no adverse events and the team is moving forward with the trial.

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This image shows a cultured Schwann cell stained for the actin cytoskeleton with phalloidin-Rd.

SCHWANN CELL:

“a cell that forms spiral layers around a myelinated nerve fiber between two nodes of Ranvier and forms the myelin sheath consisting of the inner spiral layers from which the protoplasm has been squeezed out.”   (Source)

“As a basic scientist, the hope is always to increase knowledge and discovery,” said Dietrich. “Not every day are you able to see that translated into the clinical realm with the hopes of bettering the lives of those suffering, so this Phase I clinical trial is a vital step for the field of SCI research, and for The Miami Project team that has been working diligently on this therapeutic concept for more than a quarter of a century. This trial, when completed successfully, will lay the critical foundation for future cell-based therapies to target spinal cord injuries.”

The Miami Project clinical trial will enroll a total of eight participants with acute thoracic SCI. Newly injured patients brought to the trauma center would have to meet the stringent inclusion criteria. The participants will undergo a biopsy of a sensory nerve in one leg to obtain the tissue from which to grow their own Schwann cells. The Schwann cells are then grown in a state-of-the art culturing facility for three to five weeks to generate the number of cells necessary for transplantation, and to undergo the strict purification process. By the time the Schwann cells are surgically transplanted into the injury site, participants will be 26-42 days post-injury.

All procedures will be conducted at UM/Jackson and The Miami Project to Cure Paralysis, with colleagues at the University of Miami Miller School of Medicine. Each participant will be followed intensively for one year after receiving the transplantation surgery, and their neurologic status, medical status, pain symptoms, and muscle spasticity will be evaluated. It is expected that it could be two to three years from the time the first subject is enrolled until the final subject is one year post-transplantation. All participants will continue to be monitored for an additional four years under a separate clinical protocol. This Phase I trial is the foundation upon which The Miami Project will develop future cell transplant trials targeting different types of injuries, times post-injury, and therapeutic combinations.

Posted on January 24, 2013 By Neuroscience News Featured, Neurology (Source)

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