Phenotype of HSC from Different Sources

HSC can be derived from other sources besides WBM, such as peripheral blood (PB), fetal cord blood (CB), fetal liver, skeletal muscle, and embryonic stem cells, with some pheno-typic variations. In 1951, Brechen et. al. found mice were rescued from irradiation by parabiosis with nonirradiated partners (42), suggesting that HSCs can circulate in PB. Infusion with >5 million nonirradiated PB cells also rescued irradiated mice, showing HSCs were present in the circulation at very low frequencies (43). Human PB also contains cells with primitive hematopoietic potential (44,45), although these cells are infrequent and less potent than WBM-derived HSCs (46,47). Mobilization with GM-CSF can greatly increase the frequency of HSCs in human PB (48) and is a common strategy for enriching and purifying HSCs from PB (49).

PB-derived HSCs are phenotypically distinct from WBM HSC. Although both human WBM and PB HSCs express CD34 and are RhodamineLow (50,51), mobilized PB HSCs express lower levels of c-kit than WBM HSCs (52).

HSCs are also present in newborn CB. Hematopoietic progenitors in CB have been shown to express CD34 both in vitro and in vivo (53-56). HSCs in CB are resilient to cryo-preservation and extensive handling and are therefore a clinically useful source of HSCs (57,58). CB HSCs are phenotypi-

Figure 1 Progression of cell surface marker expression on maturing murine and human HSC. Summary of cell surface markers that distinguish quiescent, activated, newly cycling, and differentiating HSCs in humans and mice.

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