Expansion of Human Megakaryocyte-biased Hematopoietic Stem Cells by Biomimetic Microniche

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 18

PMID 37072407

Authors

Yinghui Li

Mei He

Wenshan Zhang

Wei Liu

Hui Xu

Ming Yang

Hexiao Zhang

Haiwei Liang

Wenjing Li

Zhaozhao Wu

Weichao Fu

Shiqi Xu

Xiaolei Liu

Sibin Fan

Liwei Zhou

Chaoqun Wang

Lele Zhang

Yafang Li

Jiali Gu

Jingjing Yin

Yiran Zhang

Yonghui Xia

Xuemei Mao

Tao Cheng

Jun Shi

Yanan Du

Yingdai Gao

Affiliations

Soon will be listed here.

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 CD34CD38CD45RA-CD90CD49f CD62LCD133 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.

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