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Review
. 2019 Feb 18;8(2):169.
doi: 10.3390/cells8020169.

Ex Vivo Expansion of Hematopoietic Stem Cells for Therapeutic Purposes: Lessons from Development and the Niche

Parisa Tajer  1   2 , Karin Pike-Overzet  3   4 , Sagrario Arias  5 , Menzo Havenga  6 , Frank J T Staal  7   8
Affiliations
Review

Ex Vivo Expansion of Hematopoietic Stem Cells for Therapeutic Purposes: Lessons from Development and the Niche

Parisa Tajer et al. Cells. .

Abstract

Expansion of hematopoietic stem cells (HSCs) for therapeutic purposes has been a "holy grail" in the field for many years. Ex vivo expansion of HSCs can help to overcome material shortage for transplantation purposes and genetic modification protocols. In this review, we summarize improved understanding in blood development, the effect of niche and conservative signaling pathways on HSCs in mice and humans, and also advances in ex vivo culturing protocols of human HSCs with cytokines or small molecule compounds. Different expansion protocols have been tested in clinical trials. However, an optimal condition for ex vivo expansion of human HSCs still has not been found yet. Translating and implementing new findings from basic research (for instance by using genetic modification of human HSCs) into clinical protocols is crucial to improve ex vivo expansion and eventually boost stem cell gene therapy.

Keywords: clinics; ex vivo expansion; gene therapy; hematopoietic stem cell; transplantation.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Revised model for human HSC hierarchy. In the classic model for the human HSC hierarchy LT-HSCs are defined by CD34+ CD38- CD45RA- CD90+CD49f+ which differentiates into MPPS, CMPs, MLPs, GMPs. However, in a revised model, HSCs can differentiate directly into MEPs by bypassing CMP (here shown as MEP bypass route). LT-HSC: long-term hematopoietic stem cell. MLP: multipotent progenitor, CMP: common myeloid progenitor, GMP: granulocyte/macrophage progenitor, MEP: Megakaryocyte-erythrocyte progenitors.
Figure 2
Figure 2
Regulation of HSCs maintenance in niche. Different cell types are involved in promoting HSC maintenance, including perivascular stromal cells, endothelial cells (ECs), macrophages, CAR cells, sympathetic neurons by producing cytokines and growth factors such as stem cell factor (SCF), angiopoietin-1, TGF-β and notch ligands.
See this image and copyright information in PMC

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