Our Specific aims continue to explore the biology of stem cells.
Specific aim 1 uses simplified gradientseparation to isolate stem cells. We plan studies which will isolate stem cells by functional characteristics.We believe that the most primitive quiescent stem cell may not express cell surface antigens attributable tolong term engrafting cells. We have evidence that mul tipotential stem cells can proliferate and differentiateinto cells of different germ layers. We plan additional clonal a nalysis to evaluate the engraftment capacity ofpure stem cell populations. We will examine the nonhematopoieitc (epithelial) engraftment of our enrichedpopulations of marrow derived stem cells. We plan to examine the factors which are known to regulate theproliferation and differentiation of mouse adult and embryonic stem cell populations. Finally, in specific aim1, we will determine if stem cells isolated by gradient separation technology have the capacity to convertmarrow cells into epithelial tissues in response to injury signals. In the second aim, importantly, we willattempt to distinguish between the presence of tissue specific stem cells and the existence of a pluripotentstem cell which resides in the bone marrow which, when stimulated by external injury signals, will respond bymobilization to the site of injury, convert into a new germ layer, and aid in repair of the injury.RelevanceBone marrow transplantation has been utilized for hematological failure or malignancy with increasingsuccess. Recent animal models and a few clinical trials have used stem cell populations to repair injury viatransplantation. We are attempting to define the cell types which can be used for such repair, develop simpleand universal methods for isolating those cells and determining what factors in the microenvironment areresponsible for stem cell self renewal and differentiation.
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