4.1.1. Discovery

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells

The discovery of haematopoietic stem cells (HSCs) followed from experiments designed to elucidate the compromised haematopoietic system in humans exposed to irradiation after the atomic bomb explosions in World War II. The first quantitative assay for HSCs, developed by Till and McCullogh, was the Colony Forming Units – Spleen (CFU-S) assay, in which visible colonies of haematopoietic cells form in an irradiated, mostly empty, mouse spleen. This provided early quantitative data (although mostly of progenitors, rather than HSCs), but also allowed for the unequivocal demonstration, using cells with chromosomal aberrations, that all the cells in a colony, independent of lineage, are derived from a single cell. Labelling and reconstitution assays developed since (Spooncer et al., 1985; Spangrude et al., 1988) have greatly improved our ability to study these cells. The haematopoietic system is similarly sensitive to chemotherapeutic agents used to treat cancer.

HSCs have found widespread application in the clinic following pioneering work by people such as Thomas and Mathй in the late 1950s (Thomas et al., 1957; Mathй et al., 1959). Mimicking the original observation that bone marrow could rescue the haematopoietic system in an otherwise lethally irradiated recipient, bone marrow transplantation has become the standard of care for cancer patients undergoing high-dose chemo and/or radiation therapy, or suffering from haematopoietic malignancies. Globally, each year more than 50 000 people receive bone marrow transplantations (Gratwohl et al., 2010); approximately 21 000 of these are allogeneic transplants, while the remainder are autologous. In addition to bone marrow, mobilized peripheral blood or umbilical cord blood (UCB) is increasingly used as the source.


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