Stem Cells 101

By Derek A. Persons , M.D., Ph.D

Several presentations will be de-livered today in an Education Session and in a Scientific Committee Session by leaders in the field of stem cell biology that will encompass cutting-edge, fundamental issues of stem cells and their therapeutic clinical potential.

An Education Session covering Realistic Prospects for Stem Cell Therapeutics
(10:15 a.m. – 12:00 p.m. and 4:15 p.m. – 6:00 p.m.) will review data highlighting both the promises and the significant challenges of translating scientific knowledge of stem cell biology into beneficial clinical therapies. In this session, Dr. George Q. Daley will review the therapeutic potential of embryonic stem cells. Dr. Daley will discuss the likely need for directed differentiation of embryonic stem cells into therapeutically relevant cells. Diseases that may be amenable to such a cell therapy approach include neurodegenerative disorders, type I diabetes mellitus, and possibly hematopoietic disorders in instances where an appropriate hematopoietic stem cell transplant donor is not available. Dr.Margaret A. Goodell will subsequently review the potential for stem cell therapies based on adult or somatic stem cells. Whether an easily accessible stem cell source, such as bone marrow cells, could be therapeutically utilized to repair acquired damage to non-hematopoietic tissues continues to be a controversial subject for debate within the stem cell community. Dr. Goodell will review the available data that address this important issue of whether stem cells obtained from one tissue can be reprogrammed to contribute to the functional cell population of a different tissue. In the final presentation of this Education Session, Dr. Evan Y. Snyder will review the current status of neural stem cells. Importantly, he will discuss a possible roadmap to the clinic for the use of these cells.

Essential considerations in formulating a possible therapy include an in-depth knowledge of the pathophysiology of the disease process and whether it is likely that the fundamental developmental properties of neural stem cells would alter the pathophysiology. In a complementary Scientific Committee Session that will be chaired by Dr. John E. Dick, Mechanisms Controlling Stem Cell Number (8:00 a.m. – 9:45 a.m.) in vivo will be discussed. Dr.Janis L. Abokowitz will review data that support the interesting concept that hematopoietic stem cell efflux from the bone marrow may play a role in regulating the size of this stem cell compartment by acting as a “death pathway.” Dr. Abkowitz will also discuss experiments designed to estimate the number of hematopoietic stem cells in animals and in man and the implications of the findings. In a subsequent presentation, Dr. Guy Sauvageau will review recent data suggesting that manipulation of the levels of the transcription factor HOXB4 in stem cells can be utilized to profoundly influence self-renewal properties. The role of the transcription factor Pbx1 in limiting self-renewal in this pathway, as it pertains to normal homeostasis and in diseases such as leukemia, will also be discussed. Finally, the therapeutic potential of utilizing a soluble HOXB4 protein to expand hematopoietic stem cells ex vivo will be reviewed. In the final presentation of this session, Dr. Wieland B. Huttner will review studies that interrogate the mechanisms underlying the developmental switch of proliferating neuroepithelial (NE) stem cells to neuron-generating cells. Evidence supporting the possibility that the properties of the apical cell surface may serve to distinguish and perhaps define proliferating versus neuron-generating divisions of neural stem cells will be discussed. The use of RNA interference to define critical molecules involved in the function of NE stem cells will be explored.

Together, these two sessions will hold great appeal to those interested in both hematopoietic aswell as non-hematopoietic stem cells. The complexity of the field ensures that obtaining consistent and clear-cut therapeutic benefit from stem cells, outside of the context of conventional hematopoietic stem cell transplantation for hematopoietic disorders, will be a major challenge in the years to come.