6 Repopulating Patterns of Primitive Hematopoietic Stem Cells

Abstract

SIGNIFICANCE AND CLINICAL RELEVANCE
Primitive hematopoietic stem cells (PHSC) are the self-renewing precursors that regenerate myeloid and lymphoid cells throughout the life span, and they are required for successful long-term bone marrow transplantation. PHSC are found in bone marrow cells (BMC), spleen, blood, and newborn or fetal liver and blood. PHSC will be vital for putative therapeutic measures such as human gene transfer via autologous marrow cell transplantation. PHSC proliferation is required for the long-term success of clinical grafts, yet it cannot be fully defined clinically because 10–20 years may be required to recognize long-term functional cells in human beings. Fortunately, mouse PHSC appear to provide a good model for human PHSC function, and since mice are short-lived, aging about 30 times faster than humans, PHSC function over much of the life span can be studied directly.

Cells, obtained from bone marrow, cord blood, or mobilized peripheral blood of healthy donors, are clinically useful for transplantation (Barnett et al. 1994). After transplantation, donor PHSC compete with residual host PHSC for engraftment; thus, high levels of donor PHSC function are essential since host PHSC remain functional in many clinical conditions. Unfortunately, donor PHSC are often damaged by clinical manipulations, so that they repopulate less well than residual host cells. Often the most primitive cells are the most damaged (Gardner et al. 1997; Miller and Eaves 1997). Competitive repopulation directly models the donor and host stem cell competition for engraftment. One of the most important and demanding problems in hematology is...