Baffled-flow Culture System Enables the Mass Production of Megakaryocytes from Human Embryonic Stem Cells by Enhancing Mitochondrial Function

Overview

Journal Cell Prolif

Date 2023 Apr 23

PMID 37088551

Authors

Xumin Wu

Bowen Zhang

Keyi Chen

Jiahui Zhao

Yunxing Li

Jisheng Li

Chuanli Liu

Lijuan He

Tao Fan

Chao Wang

Yan Li

Xuetao Pei

Yanhua Li

Affiliations

Soon will be listed here.

Abstract

Human embryonic stem cells (hESCs) have become an ideal cell source for the ex vivo generation of megakaryocyte (MK) and platelet products for clinical applications. However, an ongoing challenge is to establish scalable culture systems to maximize the yield of stem cell-derived MKs that release platelets. We defined a specific dynamic 3D manufacturing system in a baffled-flow manner that could remarkably facilitate megakaryopoiesis and increase the yield of platelet-producing MKs from hESCs within a 12-day induction period. Additionally, an increased number of >16N ploidy MKs, proplatelets, and platelets were generated from induced cells harvested on Day 12 using the specific dynamic culture method. The specific dynamic culture method significantly enhanced endothelium-to-haematopoietic transition and early haematopoiesis. More importantly, MK fate was significantly facilitated in a specific dynamic manner during early haematopoiesis. Mechanistically, this dynamic culture significantly enhanced mitochondrial function via the oxidative phosphorylation pathway and caused differentiation skewing of hESCs toward megakaryopoiesis. This study can aid in the automatic and scalable production of MKs from stem cells using baffled-flow bioreactors and assist in the manufacturing of hESC-derived MK and platelet products.

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Baffled-flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function.

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