Blood Res.  2015 Dec;50(4):194-203. 10.5045/br.2015.50.4.194.

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough

• Park B
• Yoo KH
• Kim C

• KMID: 2133754
• DOI: http://doi.org/10.5045/br.2015.50.4.194

Abstract

Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Recently, HSCs are also spotlighted in the field of regenerative medicine for the amelioration of symptoms caused by neurodegenerative diseases, heart diseases, and others. Although the demand for HSCs has been growing, their supply often fails to meet the demand of the patients needing transplant due to a lack of histocompatible donors or a limited cell number. This review focuses on the generation and large-scale expansion of HSCs, which might overcome current limitations in the application of HSCs for clinical use. Furthermore, current proof of concept to replenish hematological homeostasis from non-hematological origin will be covered.

Keyword

HSCT; Stem cell; HLA; Blood generation; HSC expansion

MeSH Terms

Bone Marrow
Cell Count
Drug Therapy
Heart Diseases
Hematologic Diseases
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells*
Homeostasis
Humans
Metabolism, Inborn Errors
Multiple Myeloma
Neurodegenerative Diseases
Regenerative Medicine
Stem Cells
Tissue Donors

Figure

• 

  Fig. 1 HSC proliferation and engraftment ability enhanced by stem cell niche replacing components. Current usage of SR1 and Notch ligand supplemented HSC ex vivo expansion could benefit the HSC engraftment ability and epigenetic regulation.

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  Fig. 2 Schematic view of HSC expansion, non-hematological origin HSC generation, and application. Considering the current shortage of HLA-matched HSCs for patients who need allogeneic HSCT, ex vivo expanded and HLA-matched iPSC-derived HSCs could be the next generation solution. Humanized large animals could be used for the blood product generation applicable to human and for the long-term engraftment studies, because they mimic human immune complexity and might replace the artificial large scale HSC expansion.

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