Sources of Hematopoietic Stem Cells

Hematopoietic stem cell transplantation (HSCT) has the potential to cure a variety of malignant and nonmalignant diseases. Sources of hematopoietic stem cells for transplantation have expanded progressively since the beginning of the modern era of transplantation in the late 1960s. Although bone marrow was the main source of stem cells in the early years of transplantation, in the past 10 to 15 years peripheral blood has assumed increasing importance. The initial impetus for the use of PBSCs for transplantation was to be able to offer transplantation to patients who were not candidates for the use of bone marrow cells (tumor contamination of the marrow or those with hypocellular marrows). Subsequent studies demonstrated that PBSCs could be mobilized from the bone marrow with either hematopoietic growth factors (GM-CSF, G-CSF) or a combination of chemotherapy and growth factors, which increased the number of hematopoietic progenitors collected from the blood by 10to 1000fold compared with steady-state conditions. Umbilical cord blood represents the newest source of stem cells for transplantation. At now peripheral blood is the main source in the autologous setting. Within the allogeneic setting, multiple sources of stem cells are possible and include those derived from individuals related or unrelated to the patient. Hematopoietic progenitor cell (HPC) products contain hematopoietic stem and lineagecommitted progenitor cells capable of providing hematopoietic and immune reconstitution after myeloablative or reduced-intensity preparative regimens. HPCs administered intravenously migrate to the marrow, where they adhere, expand, selfrenew (stem cells only), and differentiate. The differentiated cells are released into the blood, restoring blood counts and immunity. The time from administration of HPCs to recovery of adequate or normal blood counts is variable. Recipients of peripheral blood stem cells recover counts faster than recipients of bone marrow. Cord blood tends to be the slowest to engraft. The minimum number of HPCs necessary for engraftment in a myeloablated recipient has not been established. Different products have widely different numbers of progenitors and stem cells. However, eligibility criteria for some protocols usually dictate a minimum number of cells to be collected and infused. Several methods are used to measure the number of cells in an HPC collection. Simple cell count may be adequate for many marrow collections. Most centers use flow cytometric enumeration of CD34+ cells for the majority of cellular products. The discovery of the CD34 antigen in the early 1980s revolutionized our understanding of hematopoiesis. Cells expressing CD34 are capable of reconstituting hematopoiesis in lethally irradiated animals and humans, indicating that the putative hematopoietic stem cell expresses CD34.