WEISSMAN, Irving L.: Biology, transplantation, and evolution of stem cells

Prospective hematopoietic stem cells (HSC) isolation from mouse and man reveals increased information about their characteristics upon transplantation. HSC alone can quantitatively and rapidly reconstitute the hematolymphoid system of syngeneic and allogeneic hosts, the latter without graft vs. host disease caused by contaminating T cells in bone marrow transplants. Barriers to allogeneic HSC transplants are residual host T cells that recognize foreign major histo compatibility complex molecules, their presented peptides and NK cells that detect absence of self-MHC molecules. Successful host conditioning for allogeneic HSC always eliminates both these cells. High degrees of MHC vertebrate polymorphism present formidable barriers by both T cells and NK cells. Allogeneic HSC transplants impose on hosts the immune potential of donors, including predilection for autoimmune diseases and the cells’ ability to develop immune tolerance of HSC donor host tissues, organs, and cells. Long-term reconstituting (LTR) HSC are the most primitive hematopoietic progenitors that produce multipotent short-term and non self-renewing cells. These can produce common lymphoid or myeloid progenitors, oligolineage, then single lineage committed progenitors, all of which can then be prospectively isolated in mouse and man. Isolation of these stem and progenitor cells allows the first definitive expressed gene repertoire that characterizes most developmental stages. This provides candidates for genes that control transition in a classical progression from less to more differentiated cells. We have isolated human CNS stem cells; these engraft and integrate into the mouse CNS. In a colonial protochordate somatic and germ line stem cells enter shared blood vessels of natural allogeneic chimeras where they participate in generating somatic organs and the germ line.