Stem Cell Research Panel

August 23, 2000

Medical scientists Evan Y. Snyder, M.D., Ph.D., Annemarie B. Moseley, M.D., Ph.D., and John W. McDonald, M.D., Ph.D. answer questions about advances in human stem cell research and their goals to use them in fighting conditions such as cancer, spinal cord injury, and muscle and tissue degeneration.

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BioOnline: Welcome to Bio Online's live discussion on Stem Cells! The isolation of human embryonic stem cells and the discovery that stem cells from adult organs and tissues may be more malleable than originally thought have aroused the interest of the scientific community and the public alike in the potential use of stem cells to treat a vast number of diseases. This evening, we are fortunate to have with us a distinguished group of scientists who are making significant contributions to our understanding of how to direct the differentiation of stem cells into various cell types and how to harness this knowledge for clinical use. They will discuss their own research as well as the latest significant advances in the field.

Roger Pedersen: Good evening. I'm Roger Pedersen. I will be moderating our chat event on Stem Cells for the next hour. Today is a particularly opportune time to be considering the topic of stem cells. As many of you already know, this is the day the National Institutes of Health issued its final guidelines for federal funding of stem cell research in the United States. This announcement propels stem cells into the front pages, and focuses our attention on the current status of this field of medical research, as well as it's future potential. So, what are stem cells anyway, and why should they receive so much attention? Stem cells of animals, including humans, can be thought of as the stem of a plant. They can branch into leaves, but it can also make flowers. So, the stem has all the potential of the organism. Any cell that can specialize in several different directions we refer to as having several potencies, or powers of specialization. Cells that can form several different body tissues we call pluripotent, or multipotent. It seems that pluripotent stem cells can be found throughout the life of the organism, both at very early stages (where we call them embryonic stem cells) and in the adult. We will have the chance today to talk about both kinds of stem cells, although the NIH guidelines concern themselves primarily with the stem cells that can be isolated at early stages of human development. Finally, a word about myself. I am a developmental geneticist with a focus on mammals, including mice and humans. I have been interested for many years in the unique properties of pluripotent stem cells, with their potential for use in transplantation therapy. Also, I think they can teach us a lot about how the embryo itself develops. Similarly, I think that by studying embryos of mice and other organisms, we can learn a great deal about how to control the specialization of pluripotent stem cells in the petri dish. This is the Holy Grail of the stem cell field - how to control the specialization of stem cells, and a solution to this problem will ultimately deliver the clinical promise that we all hope for. Now, I would like to introduce the panelists. We are very fortunate to have with us Evan Y. Snyder, M.D., Ph.D., Department of Neurology, Children's Hospital, Boston, Harvard Medical School. Annemarie B. Moseley, M.D., Ph.D., President and Chief Executive Officer, Osiris Therapeutics, Inc., and John W. McDonald, M.D., Ph.D., Department of Neurology and Neurological Surgery, Washington University. I'd like to have each of our panelists start by describing their interest in stem cell research. Let's start with Evan.

Evan Snyder: Our laboratory studies the biology of neural cells with stem cell properties. Approximately 14 years ago, we recognized that cells with this degree of plasticity and multipotency existed in the CNS and that such cells may represent the cellular basis for a great deal of plasticity "programmed" into the developing and even the "post-developmental" CNS; and that therapeutic advantage might be realized by the harnessing of this plasticity. Therefore, the motivation to isolate, propagate, and study neural stem cells (NSCs) is driven by 2 complementary goals. The first is to understand the processes of commitment, differentiation, and plasticity in the mammalian nervous system during development and degeneration. The second is to use such cells for therapeutic purposes. Our lab pursues these two overlapping areas of investigation - examining cells of both rodent and human origin - assuming that by understanding the biology of pluripotent neural stem cells, and by then exploiting those properties for therapeutic ends, novel strategies may emerge for redressing CNS dysfunction.

Annemarie Moseley: Osiris Therapeutics, Inc. develops cellular therapeutic products for the regeneration and functional restoration of damaged and diseased tissue. Osiris isolates, purifies and grows human mesenchymal stem cells (hMSCs), from adult bone marrow. MSCs are the progenitor cells that give rise to connective tissues, including bone marrow stroma, bone, cartilage, ligament, tendon, muscle, and fat. The stem cells are expanded over a thousand-fold from a small bone marrow aspirate and maintain their pluripotential nature. Upon infusion, implantation or injection into the body, the cells respond to the signals from the local environment, thereby naturally differentiating and integrating into the host tissue. We are conducting early clinical studies on hMSC products for the regeneration of bone marrow stroma in conjunction with allogeneic transplantation for leukemia, and regeneration of bone for both orthopedic and dental defects. In addition, we are performing preclinical studies on the use of hMSCs in joint repair and in regeneration of heart tissue after myocardial infarction (heart attack).

John McDonald: My basic science research, clinical research, and clinical practice focus is spinal cord injury. The emphasis of my lab's research is on regeneration utilizing embryonic stem cells as a strategy for neural transplantation. We are particularly focused on one aspect of regeneration - cellular replacement of oligodendrocytes - for the purpose of remyelination. Demyelination of remaining intact axons contributes to the functional loss following most spinal cord injuries, and remyelination is a pragmatic approach to restoration of meaningful function, such as improved bladder/bowel function or improved movement of a limb. We have developed methods for deriving oligodendrocytes from embryonic stem cells and we can coax them into remyelination of axons in the damaged adult nervous system.

Roger Pedersen: Welcome to our distinguished guests, and I'd like to start by asking a provocative question - mainly, with the ability to derive stem cells from adults, why is there all of this excitement about getting pluripotent stem cells from earlier stages? That is, what can pluripotent stem cells from earlier stages do that stem cells from earlier stages don't do? And I invite John, since you are a member of the embryonic stem cell club, to jump in.

John McDonald: Embryonic stem cells have received a lot of recent excitement for several reasons. One is that they represent the full developmental potential of an embryo, from essentially the beginning of a fertilized egg to, in theory, an organism, and none of the adult-derived stem cells can account for the entire developmental lineage. That means aspects of very early embryonic embryo development can be addressed with ES cells that cannot be addressed with adult derived stem cells. ES cells are also the only immortal cells, capable of dividing indefinitely, and therefore providing a continuous source of identical cells. Inherent in the first answer is that ES cells are totipotent - that is, they can make all the cells of the organism. And then finally, ES cells are one of the easiest cells to genetically manipulate. So, although today's discussions are focused on therapeutic interventions, perhaps the greatest utility of embryonic stem cells will be as a scientific tool.

Roger Pedersen: The next question, which is the counterpart of that question, is what is the excitement about adult stem cells (stem cells derived from adults), and what kinds of stem cells have been derived from adults so far?

Annemarie Moseley: I think the interest in adult stem cells has been the fact that they are able to be isolated from a number of tissue types. However, they have not been isolated from all tissue types, and in addition to the prior comments by Dr. McDonald, I want to say that the adult stem cells have not been isolated from every tissue - for instance, from lung, from pancreas, and from kidney - and it is from these areas that embryonic stem cells will have a great potential. With respect to adult stem cells, I think a lot of the interest currently has been in the fact that they are already being used clinically because they are already located in the host and they will give rise to a specifically limited amount of tissues - for instance, with the mesenchymal cells, these will give rise primarily to connective tissue. Hematopoetic stem cells give rise to multiple blood lineages, and neural stem cells have been examined that give rise predominately to neural tissues. So the use of these is going to be focused on given tissue repair and given tissue areas. The availability of the cells, I think, has generated interest in that they are often derived from the host themselves.

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