Ex vivo Expansion of Hematopoietic Stem Cells

Hematopoiesis is a complex cellular differentiation process resulting in the formation of all blood cell types. In this process, hematopoietic stem cells (HSCs) reside at the top of the hematopoiesis hierarchy and have the capacity to differentiate into all blood cell lineages (multipotency) as well as maintaining themselves (self-renewal) during the lifespan of an individual. Mouse primitive HSCs are first found in the blood islands of the extra-embryonic yolk sac at day 7.5 of gestation. At day 10.5 of gestation the earliest HSCs can be detected in the dorsal aorta region of aorta gonad mesonephros (AGM). The first HSC precursors cluster in the aortic endothelium and it has been shown that these definitive HSCs originate from specialized heamogenic endothelial cells (ECs) of the mouse embryonic aorta. Recently, it has been reported that similar to the AGM at day 10.5-11.5, ECs of mouse embryonic head also have hemogenic capacity and give rise to HSCs [5]. HSCs then migrate from these initial sources into the fetal liver around day 11, where they undergo dramatic expansion during fetal development. At next stage, around day 12 to16, HSCs are mobilized from the fetal liver into the bone marrow and spleen; although the fetal liver remains an important organ of definitive hematopoiesis during the embryonic period. From birth and throughout adult life, the bone marrow becomes the major hematopoetic tissue.

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