First Patients Receive Lab-Grown Blood Vessels from Donor Cells

First Patients Receive Lab-Grown Blood Vessels from Donor Cells

  8:07:00 PM    Science Lover

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For the first time, blood vessels created in the lab from donor skin cells were successfully implanted in patients. Functioning blood vessels that aren't rejected by the immune system could be used to make durable shunts for kidney dialysis, and potentially to improve treatment for children with heart defects and adults needing coronary or other bypass graft surgery.

Artist's rendering of blood vessels. Researchers report 
that for the first time, blood vessels created in the lab from 
donor skin cells were successfully implanted in patients. 
(Credit: © Dario Bajurin / Fotolia)

For the first time, human blood vessels grown in a laboratory from donor skin cells have been successfully implanted into patients, according to new research presented in the American Heart Association's Emerging Science Series webinar.

While more testing is needed, such "off-the-shelf" blood vessels could soon be used to improve the process and affordability of kidney dialysis.

"Our approach could allow hundreds of thousands of patients to be treated from one master cell line," said study lead author Todd N. McAllister, Ph.D., co-founder and chief executive officer of Cytograft Tissue Engineering Inc., of Novato, Calif.

The grafts also have the potential to be used in lower limb bypass to route blood around diseased arteries, to repair congenital heart defects in pediatric patients and to fix damaged arteries in soldiers, who might otherwise lose a limb, said McAllister.



The tissue-engineered blood vessels, produced from sheets of cultured skin cells rolled around temporary support structures, were used to create access shunts between arteries and veins in the arm for kidney dialysis in three patients. These shunts, which connect an artery to a vein, provide access to the blood for dialysis. The engineered vessels were about a foot long with a diameter of 4.8 millimeters.

At follow-up exams up to eight months after implantation, none of the patients had developed an immune reaction to the implants, and the vessels withstood the high pressure and frequent needle punctures required for dialysis. Shunts created from patients' own vessels or synthetic materials are notoriously prone to failure.

Investigators previously showed that using vessels individually created from a patient's own skin cells reduced the rate of shunt complications 2.4-fold over a 3-year period. The availability of off-the-shelf vessels could avoid the expense and months-long process involved in creating custom vessels for each patient, making the technique feasible for widespread use.

Besides addressing a costly and vexing problem in kidney dialysis, off-the-shelf blood vessels might someday be used instead of harvesting patients' own vessels for bypass surgery. A larger, randomized trial of the grafts is under way for kidney dialysis, and human trials have been initiated to assess the safety and effectiveness of these grafts for lower-limb bypass.

The study will be presented in the American Heart Association's Emerging Science Series, which will be held at 1 p.m. EDT/ 12 p.m. CDT. The series is a free online webinar presentation of cutting-edge science. The Emerging Science Series provides a new venue for presenting the latest cardiovascular scientific breakthroughs several times a year, when the discoveries are ready to be presented rather than waiting for a regularly scheduled meeting. Each study is handled in a peer-reviewed process similar to late-breaking clinical trials presented at AHA's annual Scientific Sessions.

The series will include the first presentation of data from clinical trials, basic science, key updates of previously presented trials and major bench-to-bedside breakthroughs.

Co-authors are Wojciech Wystrychowski, M.D.; Lech Cierpka, M.D.; Krzysztof Zagalski, M.D.; Sergio A. Garrido, M.D.; Samuel Radochonski, B.S.; Nathalie Dusserre, Ph.D.; and Nicholas L'Heureux, Ph.D.

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New Genetic Technique Converts Skin Cells Into Brain Cells

New Genetic Technique Converts Skin Cells Into Brain Cells

  6:16:00 PM    Science Lover

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A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells; genes which are already known to be active in the formation of brain cells at the fetal stage.

Photomicrograph of fibroblast cells in tissue culture. 
(Credit: iStockphoto/Torsten Wittmann)

The new technique avoids many of the ethical dilemmas that stem cell research has faced.

For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.

Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.

"We didn't really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions." The study, which was published in the latest issue of the Proceedings of the National Academy of Sciences, also shows that the skin cells can be directed to become certain types of nerve cells.

In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson's disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.



Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.

Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body's immune system than transplanted cells from donor tissue.

"This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson's disease," says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.

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New genetic technique converts skin cells into brain cells

New genetic technique converts skin cells into brain cells

  12:34:00 AM    Science Lover

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A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells; genes which are already known to be active in the formation of brain cells at the foetal stage.

converts skin cells into brain cells

The new technique avoids many of the ethical dilemmas that stem cell research has faced.

For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.

Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.

"We didn't really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions."

The study, which was published in the latest issue of the scientific journal PNAS, also shows that the skin cells can be directed to become certain types of nerve cells.

In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson's disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.

Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.

Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body's immune system than transplanted cells from donor tissue.

"This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson's disease", says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.

More information: 'Direct conversion of human fibroblasts to dopaminergic neurons', publ. PNAS 2011; 6 June 2011: http://www.pnas.or … 108.abstract

Provided by Lund University

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