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Review
. 2022 Aug 1;14(8):a040774.
doi: 10.1101/cshperspect.a040774.

Hematopoietic Stem Cells and Regeneration

Mitch Biermann  1 , Tannishtha Reya  1   2
Affiliations
Review

Hematopoietic Stem Cells and Regeneration

Mitch Biermann et al. Cold Spring Harb Perspect Biol. .

Abstract

Hematopoietic stem cell (HSC) regeneration is the remarkable process by which extremely rare, normally inactive cells of the bone marrow can replace an entire organ if called to do so by injury or harnessed by transplantation. HSC research is arguably the first quantitative single-cell science and the foundation of adult stem cell biology. Bone marrow transplant is the oldest and most refined technique of regenerative medicine. Here we review the intertwined history of the discovery of HSCs and bone marrow transplant, the molecular and cellular mechanisms of HSC self-renewal, and the use of HSCs and their derivatives for cell therapy.

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Figures

Figure 1.
Figure 1.
Timeline of hematopoietic stem cell (HSC) and blood marrow transplant (BMT) discoveries. (HSCT) Hematopoietic stem cell transplant, (SCID) severe combined immunodeficiency, (ST-HSC) short-term HSC, (LT-HSC) long-term HSC, (iPS) induced pluripotent stem cells, (HLA) human leukocyte antigen, (CAR) chimeric antigen receptor.
Figure 2.
Figure 2.
Factors promoting hematopoietic stem cell (HSC) dormancy and proliferation. (SCF) Stem cell factor, (TPO) Thrombopoietin, (PVA) polyvinyl alcohol.
Figure 3.
Figure 3.
Current blood marrow transplant (BMT) indications separated by source of donor hematopoietic stem cells (HSCs) (autologous vs. allogeneic). (MM) Multiple myeloma, (NHL) non-Hodgkin lymphoma, (AML) acute myeloid leukemia, (MDS) myelodysplastic syndromes, (ALL) acute lymphocytic leukemia, (HL) Hodgkin's lymphoma, (CML) chronic myeloid lymphoma. Benign disorders include bone marrow failure syndromes such as aplastic anemia, congenital diseases, and other nonmalignant conditions. (Figure adapted from Phelan et al. 2020. Full complement of slides related to this figure are available at www.cibmtr.org.)
Figure 4.
Figure 4.
Process of the creation of patient-specific iPS stem cells, genetic correction, and differentiation to hematopoietic stem cells (HSCs) for the treatment of hematological genetic diseases (such as sickle cell anemia). (BMT) Bone marrow transplant, (iPS) induced pluripotent stem cells.
Figure 5.
Figure 5.
Creation of patient-specific chimeric antigen receptor (CAR) T-cell therapy, in which patient T cells after delivery of the CAR cassette—a synthetic transmembrane (TM) receptor recombining multiple functional domains (inset, right)—can target cells bearing tumor-specific antigens. (scFv) Single-chain variable fragment.
See this image and copyright information in PMC

References

    1. Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, Cowin BL, Bruner E, Murphy MM, Chen W, et al. 2017. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature 549: 476–481. 10.1038/nature23876 - DOI - PMC - PubMed
    1. Akunuru S, Geiger H. 2016. Aging, clonality, and rejuvenation of hematopoietic stem cells. Trends Mol Med 22: 701–712. 10.1016/j.molmed.2016.06.003 - DOI - PMC - PubMed
    1. Amabile G, Welner RS, Nombela-Arrieta C, D'Alise AM, Di Ruscio A, Ebralidze AK, Kraytsberg Y, Ye M, Kocher O, Neuberg DS, et al. 2013. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood 121: 1255–1264. 10.1182/blood-2012-06-434407 - DOI - PMC - PubMed
    1. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, et al. 2012. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 367: 1487–1496. 10.1056/NEJMoa1203517 - DOI - PMC - PubMed
    1. Antonchuk J, Sauvageau G, Humphries RK. 2002. HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 109: 39–45. 10.1016/S0092-8674(02)00697-9 - DOI - PubMed

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