Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche

Abstract

Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.

Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network

“…This, to some extent, also influences the bias of HSC lineage differentiation. In other words, HSCs situated in a specific ecological niche are only capable of receiving particular stimuli and then differentiate toward the lineage to which they are biased [ 22 , 23 ]. Moreover, a recent study revealed the origin of heterogeneity in zebrafish embryonic hematopoietic stem progenitor cells.…”

Synergistic effect and molecular mechanism of nicotinamide and UM171 in ex vivo expansion of long-term hematopoietic stem cells

“…In this study, we investigated the effect of the combination of NAM and UM171 on HSC expansion ex vivo . In humans, CD34+CD38-cells are classic HSPCs, and HSCs can be functionally divided into ST-HSCs (CD34+CD38-CD45RA-CD49f+CD90-) and LT-HSCs (CD34+CD38-CD45RA-CD49f+CD90+) [ [14] , [15] , [16] , [17] , [18] , [19] , [20] ]. We found that NAM+UM171 exhibited superior activity in expanding phenotype defined LT-HSCs proportionally and quantitatively, the expansion folds of LT-HSCs reached 753.16 ± 83.02.…”