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In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation - PubMed

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Review

In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation

Yavor K Bozhilov et al. Cells. 2023.

Abstract

The haematopoietic system plays an essential role in our health and survival. It is comprised of a range of mature blood and immune cell types, including oxygen-carrying erythrocytes, platelet-producing megakaryocytes and infection-fighting myeloid and lymphoid cells. Self-renewing multipotent haematopoietic stem cells (HSCs) and a range of intermediate haematopoietic progenitor cell types differentiate into these mature cell types to continuously support haematopoietic system homeostasis throughout life. This process of haematopoiesis is tightly regulated in vivo and primarily takes place in the bone marrow. Over the years, a range of in vitro culture systems have been developed, either to expand haematopoietic stem and progenitor cells or to differentiate them into the various haematopoietic lineages, based on the use of recombinant cytokines, co-culture systems and/or small molecules. These approaches provide important tractable models to study human haematopoiesis in vitro. Additionally, haematopoietic cell culture systems are being developed and clinical tested as a source of cell products for transplantation and transfusion medicine. This review discusses the in vitro culture protocols for human HSC expansion and differentiation, and summarises the key factors involved in these biological processes.

Keywords: B cell; T cell; differentiation; erythrocyte; expansion; haematopoiesis; haematopoietic stem cells; in vitro; megakaryocyte; monocyte; neutrophil; self-renewal.

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Conflict of interest statement

ACW is a consultant for Graphite Bio and ImmuneBridge. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Key factors and pathways involved in haematopoietic stem cell self-renewal and differentiation. Haematopoietic stem cells (HSCs) can either self-renew to generate more HSCs or differentiate into the megakaryocyte, erythroid, myeloid (including neutrophil and monocyte) or lymphoid cell (including B cell and T cell) lineages. The key cytokine signalling pathways and transcription factors that regulate HSC self-renewal and differentiation are summarised. This figure was created using

www.Biorender.com

.

Figure 2
Figure 2

Timeline of culture conditions for improving HSC expansion. This figure was created using Microsoft PowerPoint.

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References

    1. Boulais P.E., Frenette P.S. Making Sense of Hematopoietic Stem Cell Niches. Blood. 2015;125:2621–2629. doi: 10.1182/blood-2014-09-570192. - DOI - PMC - PubMed
    1. Pinho S., Frenette P.S. Haematopoietic Stem Cell Activity and Interactions with the Niche. Nat. Rev. Mol. Cell Biol. 2019;20:303–320. doi: 10.1038/s41580-019-0103-9. - DOI - PMC - PubMed
    1. Morrison S.J., Scadden D.T. The Bone Marrow Niche for Haematopoietic Stem Cells. Nature. 2014;505:327–334. doi: 10.1038/nature12984. - DOI - PMC - PubMed
    1. Notta F., Doulatov S., Laurenti E., Poeppl A., Jurisica I., Dick J.E. Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment. Science. 2011;333:218–221. doi: 10.1126/science.1201219. - DOI - PubMed
    1. Laurenti E., Göttgens B. From Haematopoietic Stem Cells to Complex Differentiation Landscapes. Nature. 2018;553:418–426. doi: 10.1038/nature25022. - DOI - PMC - PubMed

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Grants and funding

We acknowledge funding support from the Kay Kendall Leukaemia Fund (Grant Number KKL1378), the National Institute of Health Research (NIHR) Oxford-Birmingham Blood and Transplant Research Unit in Advanced Cellular Therapies, the NIHR Oxford Biomedical Research Centre, the John Fell Fund, and the Christopher Welch Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.