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Equine Stem Cell Research
Article by: The Grayson- Jockey Club Research Foundation, Inc.
http://www.grayson-jockeyclub.org
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Manipulation of stem cells is recognized as important for present and future developments in both human medicine and veterinary medicine. Research currently funded by Grayson-Jockey Club Research Foundation includes Dr. Lisa Fortier’s project at Cornell University, entitled Patient Side Constructs for Cartilage Regeneration.
Dr. Fortier, DVM, PhD, Diplomate ACVS, here answers questions on the realities and potentials of stem cell research.

Question – The fact that cells exist that can be guided into specified roles has a science-fiction ring to it to the layman. (Dr. Frankenstein would have loved this!) Can you trace roughly how and when that knowledge was developed? Did it originate in human medicine or veterinary medicine?

Dr. Fortier – Stem cells were identified in the bone marrow of mice in the early 1960s. Very quickly thereafter, stem cell therapy for leukemia was implemented in people. The use of stem cells from bone marrow for replenishing blood cells after chemotherapy or radiation therapy is still the most widely used application of stem cell therapy and is accepted standard medicine practice. In equine veterinary medicine, stem cell therapy was first used in the early 1990s by Dr. Doug Herthel of Alamo Pintado Equine Medical Center. He pioneered the use of bone marrow aspirates to treat tendon and suspensory ligament injuries in horses.

Question> – In human medicine, the use of embryonic stem cells is a point of ethical debate. As we understand it, stem cells from the chest of adult horses are, or have been, preferable. Can you discuss the differences? Is one more “malleable” than another?

Dr. Fortier – Recent (November 2007) breakthroughs in embryonic stem cells demonstrate that adult cells can be converted to embryonic stem cells without the creation or destruction of an embryo, so the ethical controversies surrounding the use of embryonic stem cells will diminish substantially. Embryonic stem cells are more "malleable" in that they divide more readily and can turn into nerve better than adult-derived stem cells; but, they are also harder to control.

Question – Some stem cell research involved an experiment with use of fatty stem cells from the root of the tail. Did this turn out to be viable?

Dr. Fortier – Several research groups are working on fat, bone marrow, and umbilical cord-derived stem cells. We still do not know which source provides the greatest number or the most malleable stem cells.

Question – What is the procedure for taking a stem cell and causing it to form into the kind of cell you want it to?

Dr. Fortier – For each type of tissue that you are trying to form, there are a set of proteins (growth factors) and cues from the environment that will direct a stem cell into a certain cell type. The exact recipe is not known, but there are general guidelines.

Question – What are some of the categories of cells that a stem cell can be made to become?

Dr. Fortier – Adult-derived stem cells, such as those from fat or bone marrow, can become cartilage, bone, and fat. Embryonic stem cells can become all cell types.

Question – Is there any fear that a stem cell guided to become a certain cell – let’s call it an A cell – will be inferior to a cell that started out as an A cell? Is the answer different according to what function the cell is asked to fill?

Dr. Fortier – The hope is that the stem cell which is directed to become an "A cell" will be superior to an existing "A cell" because it will essentially be a younger cell and therefore more likely to aid in the healing process.

Question – Damage to cartilage is a major problem because cartilage is never replaced. Is stem cell treatment a possible solution to cartilage repair?

Dr. Fortier – Absolutely, and there are many research groups working on this exact concept. Stem cell treatment could potentially be applied to any disease where there is cell damage or cell loss; such as cartilage damage, tendonitis, and laminitis.

Question – In your recent presentation at the American Association of Equine Practitioners’ convention, you warned against pie-in-the-sky expectations for stem cell therapy. What are some of the uses that you think can be achieved in the short and medium term future?

Dr. Fortier – An important aspect to new therapeutics is having a good outcome measure. For tendon or cartilage damage, our outcome measure is typically resolution of lameness, return to athletic soundness, and less re-injury compared to conventional therapies. The AAEP presentation warned against the promise of stem cell therapy for problems such as laminitis, for which there are few good outcome measures and therefore no convincing way to demonstrate efficacy of treatment.

Question – Notwithstanding the fact that stem cell treatment of tendons is not a proven cure, can you describe the procedure of trying this? Are stem cells grown in vitro and then injected into the tendon?

Dr. Fortier – There are three main ways that stem cells are presently being used to treat tendonitis. First, there is application of bone marrow stem cells, concentrated via centrifugation, and injected into the lesion 15 minutes later. The advantage of this technique is that it can be applied at the time of diagnosis; the disadvantage is that fewer stem cells are obtained as compared to the other two methods. Second, there is the culture of stem cells from bone marrow aspirate. The advantage of this technique is that more stem cells can be delivered; the disadvantage is that it takes a couple of weeks to grow the stem cells, and there is fairly good evidence that earlier treatment is better.
Finally, there is the use of stem cells from fat. The advantage of this technique is that you get more cells (like the second technique), it only takes two days to get the cells from the fat (so is in between methods one and two). The disadvantage is that a surgical approach is needed to obtain the fat, and it is not patient-side like the first method. Patient-side or point-of-care methods are those that can be applied immediately to the patient; no laboratory manipulations are required. There are no long term or randomized clinical studies to determine which of these treatments is superior.

Question – Can you describe for us the work you personally have done with stem cells and your short-term goals?

Dr. Fortier – Several years ago, we attempted to establish equine embryonic stem cells, but were unable to obtain enough cells to investigate their therapeutic potential. Our current work, funded by the Grayson-Jockey Club, is to better characterize what defines a true stem cell from bone marrow or fat.
Concurrently, we are working on developing patient-side techniques for cartilage repair and tendon or suspensory ligament regeneration. At the recent AAEP meeting in Orlando, we presented our research data on the concentration of stem cells for cartilage repair and the results are very promising.

Question – Has public discussion about stem cells in human medicine had any effect, positive or negative, on the momentum of stem cell research in veterinary medicine?

Dr. Fortier – The retraction of the human embryonic stem cell paper from Hwang in 2006 certainly diminished enthusiasm for embryonic stem cell research, but the two new breakthroughs in November of this year have resurrected and reinvigorated embryonic stem cell work. In human beings, there is promising preliminary data on the recovery of stroke victims after stem cell injection.
The very exciting part of this story is that the stem cells appear to be attracted to the damaged heart and they function as factories to secrete proteins to help repair the damaged heart and to recruit new cells and they are not functioning as beating heart cells. This would imply that the cells can seek out damaged tissue, and that perhaps complete replenishment of all the cells in a tissue is not necessary.

Question – Would you care to make any predictions on what the next 10 years can bring in stem cell research if funding is sufficient?

Dr. Fortier – In general, the field of stem cell research is still in its infancy. In the next 10 years, I would envision that we will know how to identify, recruit, and manipulate the stem cells that naturally reside within every tissue in order to enhance tissue regeneration.

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