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Skin Cells As Stem Cells

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Photo Credit: Ivanhoe Photo Credit: Ivanhoe
Photo Credit: Ivanhoe Photo Credit: Ivanhoe

SAN FRANCISCO, CA (Ivanhoe Newswire) - Stem cells, they could hold the key to the treatment and cure of more than 70 major diseases and conditions. A science lab is taking stem cell technology another step into the future.

From broken hearts to severed spines to damaged brains. The answer to heal them all may be found inside a lab.

"One artery was completely blocked," Elmer Goodman, a heart disease patient, told Ivanhoe.

"It was just like somebody took a tarp from the bottom of my neck and just peeled it back and took all the feeling from me," John Miksa, who is paralyzed, said.

"I was going to be drooling on a bib, in a wheelchair for the rest of my life," Erwin Velbis, a stroke survivor, said.

"We had a major breakthrough," Deepak Srivastava, M.D., from the Gladstone Institute of Cardiovascular Disease, said.

Doctor Deepak Srivastava and doctor Sheng Ding are two of the many minds at Gladstone Institute using not adult stem cells or embryonic stem cells, but your own skin cells to repair bodies from the inside out.

"It means in the future one might be able to create new heart cells, new lung cells, new spinal cord cells, starting with your own cells from your skin," Dr. Srivastava said.

Doctor Srivastava is taking adult skin cells, and turning them into beating heart cells. It's called direct reprogramming.

"We've been able to create a beating heart cells that used to be on someone's skin…which is really like science fiction," Dr. Srivastava said.

The same approach could be used to repair spinal cord injuries and practically any other part of the body.

"We've been working on new methods that can convert cells from the skin to brain cells," Sheng Ding, Ph.D., at the Gladstone institute, said.

Doctor Ding has transformed the adult skin cells into neurons that are capable of transmitting brain signals. They hope this could reverse the effects of Alzheimer's, Parkinson's and stroke.

"It's the ultimate in personalized medicine," Dr. Srivastava said.

Doctors say because they're using a patient's own skin cells, there's little to no chance of rejection. These skin cells could also be used to test new drugs and each patient's possible response to those drugs. Allowing doctors to better personalize medicine.

RESEARCH SUMMARY:

BACKGROUND: Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated. Under the right conditions, stem cells divide to form more cells, called daughter cells. These daughter cells become new stem cells or specialized cells with a more specific function, such as blood cells, brain cells, heart muscle or bone. Stem cells are unique — no other cell in the body has the natural ability to generate new cell types. Researchers have discovered several sources of stem cells.

  • Embryonic stem cells come from embryos that are four to five days old. They can divide into more stem cells or become any type of body cell. Because of this versatility, embryonic stem cells have the highest potential to regenerate or repair diseased tissue and organs.
  • Adult stem cells are found in small numbers in most adult tissues. They are also found in children, placentas and umbilical cords. Until recently, it was believed that they could only create similar types of cells. For instance, it was thought that stem cells in bone marrow could give rise only to blood cells. However, emerging evidence suggests that adult stem cells may be able to create unrelated types of cells. For instance, bone marrow stem cells may be able to create muscle cells.
  • Adult cells altered to have properties of embryonic stem cells through nuclear reprogramming. Scientists have successfully transformed adult cells into stem cells using this technique. By altering genes in adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells. It's not known if this will cause adverse effects in humans.
  • Amniotic fluid stem cells are found in the fluid that fills the sac surrounding a developing fetus in the uterus. More study of amniotic fluid stem cells is needed to understand their potential.

(www.mayoclinic.com)

DIRECT REPROGRAMMING: A goal of regenerative medicine has been to take any cell from a person's body and turn it in to any other cell type that may be desired. This would eliminate several donor-compatibility problems, and potentially eliminate the need for a donor. Much progress has been made in direct reprogramming with muscle, blood, the pancreas, and neurons. There are many degrees of direct reprogramming that have been reported. Several progenitor cells, cells that appear committed to their fate, but not fully differentiated, have been shown to be capable of differentiating into a different cell type; this process is called transdetermination. However, in a few cases a fully differentiated cell can actually become a different cell type; this process is called transdifferentiation (Graf and Enver, 2009). (www.allthingsstemcell.com)

GLADSTONE INSTITUTE: The J. David Gladstone Institutes is an independent, nonprofit biomedical research institution affiliated with the University of California, San Francisco (UCSF), devoted to research into cardiovascular disease, viral infections and neurological disorders. Gladstone is composed of three institutes: The Institute of Cardiovascular Disease, which opened in 1979; the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. While independent, Gladstone is formally affiliated with UCSF. Gladstone investigators participate in many university activities, including the teaching and training of graduate students.

INTERVIEW

Dr. Srivastava, Director and Senior Investigator at Gladstone Institute of Cardiovascular Disease, discusses growing your own skin cells to generate stem cells for future use in repairing damaged heart muscle as well as brain and spinal repair.

You are talking about Alzheimer's and Parkinson's; you're looking at ways to impact both of those diseases?

Dr. Srivastava: One of the most devastating groups of diseases that face the United States and most of the world in the coming decades are those that involve the brain, including degenerative diseases such as Alzheimer's, Parkinson's and Huntington's Disease. And right now we have very few options for patients with these diseases that rob individuals of their dignity and their functioning livelihood. We're very hopeful that stem cells could make an enormous difference for those people in the coming years and we have to be able to find ways to replace brain cells that are being killed and make them function the way they should be.

So talk about Alzheimer's and Parkinson's.

Dr.Srivastava: Degenerative diseases of the brain are one of the biggest hurdles that the society will face in the coming years. One out of six people are expected to get Alzheimer's disease above the age of sixty-five and right now we have very little treatment for any of these individuals. So we have great hope that a stem cell approach where we can create new brain cells to replace the ones that have died can offer hope for these individuals so that they once again can live a functioning life.

Tell me about tracking cardiovascular disease in families.

Dr. Srivastava: One of the ways we've tried to understand the causes of various cardiac disorders is to identify large families over multiple generations who share a common disease. That allows us to find a single gene that is affected in the family that causes the disorder, and we've been able to do that for several different families. We've now made stem cells using skin cells from those individuals to try to understand how the disease occurs and try to test new therapeutic approaches in cells in a dish to find new cures. We're very excited that we will be able to use this stem cell-based model of human disease to find new drugs that could address some of the diseases that right now have no treatment.

How long have you been working on the stem cells?

Dr. Srivastava: We've been studying the issue of how an embryonic cell becomes a heart cell or brain cell or other type of adult cell for the last twenty years. And it's only in the last six or seven years that we've been able to leverage much of that knowledge on stem cells in a dish.

Why has it taken so long, it seems like all at once everybody is using stem cells now? Why all at once in the last five to seven years?

Dr. Srivastava: We've been studying stem cells for the last fifteen to twenty years and only more recently has the technology really allowed us to think about how we could actually treat patients and find cures for diseases using stem cells.

With the discovery of the genome did that help?

Dr. Srivastava: It's a variety of things, the explosion of recent years I think has been partly because of the iPS discovery the new skin-derived stem cell discovery. It's only been ten years since we could even grow human stem cells in a dish, embryonic stem cells. So it's only really in the last five years to seven years we've known enough to be able to control those cells and tell them to do what we want them to do.

Does it seem like it's been a long road but there's a light at the end of the tunnel now?

Dr. Srivastava: It seems like things have been moving really fast and the light is getting brighter and brighter.

So you are using a person's own skin cells to help regenerate?

Dr. Srivastava: The problem with most human diseases is that when you lose some cells in an organ then we don't have the ability to regenerate that organ and replace those dead stem cells. And so the net result is that people need transplants or they just ultimately die from their various diseases. And what we're trying to do here at Gladstone is find new ways to generate replacement organs or parts of the organs to be able to address people who have lost parts of their organs.

And you are doing a lot of this with skin cells?

Dr. Srivastava: We had a major breakthrough from one of our investigators here at Gladstone several years ago where Dr. Yamanaka found a way to take a skin cell from an adult and convert that cell into one that behaved just like an embryonic stem cell, in that it could turn in to all the different cells types of the human body. The discovery bypassed the ethical debate around the use of human embryonic stem cells, and it also provided a new way to think about regenerating organs with one's own cells so that it would be genetically matched and not be rejected by the immune system.

What does this mean for people?

Dr. Srivastava: It means that in the future one might be able to create new heart cells, new brain cells, new spinal cord cells starting with your own cells from your skin. And so there's a tremendous hope in the field that this new approach, which doesn't have any ethical barriers, is going to be one that revolutionizes regenerative medicine.

And you've been able to create a beating heart cell?

Dr. Srivastava: We've been able to create a beating heart cell that used to be on somebody's skin, which is really like science fiction, but we're really able to do that quite efficiently now. And the next hurdle for us is really to be able to engineer these cells in a three-dimensional fashion so that they can contribute to a functioning heart.

How far away are you from people?

Dr. Srivastava: I think the approach that requires a tissue engineering approach is still probably at least five years away before we're ready for clinical trials, for the heart at least. There's a new approach that we've taken that builds on this idea that we can change the fate of a cell at will. And what we've been able to do most recently, that I'm most excited about, is take cells that are in a heart already that are not muscle and they don't beat, and we've found a way to genetically engineer those cells so that they switch their fate and become beating heart cells. And the beauty of this is that these cells are already in the organ. If we introduce just a few genes or factors into the heart, then we can regenerate the heart from within an organ and not even have to put any cells in to the organ. And so this new approach to regenerative medicine, by harnessing cells that are already in the organ, has fewer barriers and we are hoping that just in the next few years we'll be in a position to start clinical trials to regenerate the heart with this new approach.

What's the difference between this and the trial I was telling you about where they put stem cells in to the heart and they grow new vessels kind of like a natural bypass?

Dr. Srivastava: That approach involves potentially creating new blood vessels and that can be useful. The real problem though for the millions of people who suffer heart attacks around the world is that their muscle cells die and when heart muscle dies it can't be regenerated. So you can give it new blood vessels, but you're not really changing the fact that there's less heart muscle available. And the real key is to regenerate new muscle and that's where this approach is quite different.

And it just doesn't stop with the heart you have other organs that you're concentrating on?

Dr. Srivastava: We think the same approach can be used for many different organs in the body. At Gladstone we have a major focus also on the brain and the spinal cord and we think that the same approach could be also used to regenerate brain cells and spinal cord cells after injury.

Can you talk about the skin cells to brain cells?

Dr. Srivastava: Investigators at Gladstone have found a way to change the fate of skin cells either into new brain cells or even into a brain stem cell state where we can expand brain stem cells to get larger numbers that might be required for regenerative therapy.

So what would that mean for patients?

Dr. Srivastava: The patients that we focus on at Gladstone involve those who have heart disease and also brain diseases who could benefit from regenerative medicine. Every minute in the United States there's a new person who has a heart attack and loses part of their heart muscle. Ultimately they end up in a situation where they can't walk up a flight of stairs, they can't walk from the parking lot to their place of work and what we hope our work will mean for them is that they will have new heart muscle again that will allow them to function and live a more normal life.

How long does it take to convert a skin cell to a heart muscle?

Dr. Srivastava: It depends on how we do it - it can take a few weeks but what we've found is that the process can start within a few days. And so, at least in a mouse, we find that within two to four weeks we're able to convert cells in the heart that are not muscle in to new muscle.

How do you do that, do you inject the heart with the new cells?

Dr. Srivastava: The approach that we are taking is actually a gene therapy approach where we would inject three or four genes into the heart, without even having to put any cells in, and those genes would be powerful enough to convert non-muscle cells into new muscle. And the same approach we think can be taken with brain or spinal cord cells where we can inject genes into that area that would convert the cells that are already there into new cells that could be useful.

So this is the ultimate in personalized medicine, you're not relying on anybody but yourself?

Dr. Srivastava: That's right it's the ultimate personalized medicine.

FOR MORE INFORMATION, PLEASE CONTACT:

Gladstone Press Relations
(415) 734 5000

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