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

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 (low)CD62L(-)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. An effective expansion system for therapeutic megakaryocyte-biased hematopoietic stem cells has not been developed. Here the authors present a microniche-based system that supports scalable expansion of human Mk-biased HSCs and identify their immune phenotype.

Automated summary

This study presents a biomimetic microniche-based system for expanding human hematopoietic stem cells (HSCs), particularly megakaryocyte-biased HSCs. The expansion of HSCs was demonstrated from various sources using this system, and scalability was achieved in a stirred bioreactor. Furthermore, the study identifies a specific immune phenotype for the expanded megakaryocyte-biased HSCs. This research provides a flexible HSC expansion strategy and contributes to the understanding and potential clinical application of HSC-based therapies.