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Sources of hematopoietic stem cells

Robert S Negrin, MD
Section Editor
Nelson J Chao, MD
Deputy Editor
Alan G Rosmarin, MD


Hematopoietic cell transplantation (HCT) is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant diseases. The multipotent hematopoietic stem cells required for this procedure are usually obtained from the bone marrow or peripheral blood of a related or unrelated donor. Umbilical cord blood, the blood remaining in the umbilical cord and placenta following the birth of an infant, has emerged as an established alternative source of hematopoietic stem cells in allogeneic HCT.

This topic review will discuss the hematopoietic stem cell model of hematopoiesis followed by a discussion of the sources of hematopoietic cells suitable for transplantation. The selection of an appropriate HCT donor, the evaluation of a potential HCT donor, and the collection of umbilical cord blood are discussed separately. (See "Donor selection for hematopoietic cell transplantation" and "Evaluation of the hematopoietic cell transplantation donor" and "Collection and storage of umbilical cord blood for hematopoietic cell transplantation" and "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor/hematopoietic stem cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood progenitor cell transplantation). (See 'Sources of hematopoietic stem cells' below.)


Discovery of HSCs — Hematopoiesis is sustained throughout the lifespan of an individual by a small number of multipotent hematopoietic stem cells that slowly cycle from a larger quiescent pool. Circulating blood cells are immediate descendants of maturing precursors that arise from a smaller pool of progenitors. The progenitors in turn arise from an even smaller pool of hematopoietic stem cells (HSC). HSCs are multipotent and have the capacity to differentiate into the cells of all blood lineages: erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, T and B lymphocytes, natural killer cells, and dendritic cells (figure 1).

The identification and role of HSCs in protecting animals from lethal irradiation emerged from studies that began in the 1950s in which it was observed that animals treated with irradiation could be protected by either lead shielding over the spleen or later infusion of splenocytes from a normal donor. With the development of in vitro and in vivo assay systems (eg, Till-McCulloch spleen-colony assay) it became clear that there were clonotypic precursor cells capable of giving rise to both erythroid and myeloid lineages of cells [1]. HSCs were defined functionally as populations of cells capable of rescuing lethally-irradiated animals, a definition that is accurate conceptually, although difficult to apply in different systems, especially in humans. Nevertheless, it became possible to define a population of cells capable of multilineage repopulation and rescuing animals from lethal irradiation. These hematopoietic stem cells could be re-isolated and used to rescue other lethally irradiated animals. (See "Overview of hematopoiesis and stem cell function".)


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