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Chemically defined cytokine-free expansion of human haematopoietic stem cells
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Chemically defined cytokine-free expansion of human haematopoietic stem cells
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Journal Article
Chemically defined cytokine-free expansion of human haematopoietic stem cells
2023
Overview
Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases
1
,
2
. However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation
3
. Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo
4
. Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies.
A culture system allows the long-term expansion of human haematopoietic stem cells (HSCs) in vivo without the use of recombinant cytokines or albumin, with potential applications for clinical therapies involving HSCs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/100
/ 13/31
/ 38/91
/ 64/60
/ Agonists
/ Albumins
/ Blood
/ Cell Culture Techniques - methods
/ Cell Proliferation - drug effects
/ Culture
/ Hematopoietic Stem Cell Transplantation
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - drug effects
/ Hematopoietic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Phosphatidylinositol 3-Kinases - metabolism
/ Polymers
/ Reagents
/ Science
/ Single-Cell Gene Expression Analysis
