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Mechanistic Basis of ex Vivo Umbilical Cord Blood Stem Progenitor Cell Expansion.

Authors
  • Sica, R Alejandro1
  • Terzioglu, Meryem K1
  • Mahmud, Dolores1
  • Mahmud, Nadim2, 3
  • 1 Division of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine Chicago, 840 South Wood Street, Clinical Sciences Building (CSB) Rm# 826, Chicago, IL, 60612, USA.
  • 2 Division of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine Chicago, 840 South Wood Street, Clinical Sciences Building (CSB) Rm# 826, Chicago, IL, 60612, USA. [email protected]
  • 3 University of Illinois Cancer Center, Chicago, IL, USA. [email protected]
Type
Published Article
Journal
Stem cell reviews and reports
Publication Date
Aug 01, 2020
Volume
16
Issue
4
Pages
628–638
Identifiers
DOI: 10.1007/s12015-020-09981-w
PMID: 32424674
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Umbilical cord blood (CB) transplantation has been used successfully in humans for three decades due to its rapid availability for patients lacking a suitable allogeneic donor, less stringent HLA matching requirements, and low rates of relapse and chronic graft-versus-host disease (GVHD). However, CB transplantation is associated with complications, such as delayed hematopoietic engraftment, graft failure, which increases infection and bleeding and causes longer hospital stays, and transplant-related mortality. The majority of these biological limitations are due to the unforeseeable functional potency of multipotent hematopoietic stem cells (HSCs), which reduce the predictability of successful transplantation; however, several strategies have been developed to increase the number of hematopoietic stem progenitor cells (HSPCs) infused during CB transplantation. This review primarily addresses the methods that promote ex vivo CB expansion within the context of symmetrical and asymmetrical HSC division and those that rely on epigenetic mechanisms, along with the reportedly most successful cytokine combinations. We also review recent clinical research on small molecules (StemRegenin-1, UM171, and nicotinamide) in ex vivo expanded CB and discuss yet unvalidated preclinical strategies. Expanding and transplanting CB graft enriched in HSPCs in a single CB unit is a particularly exciting prospect with the potential to improve the use and availability of CB grafts. Greater knowledge of optimal ex vivo expansion strategies, cell longevity, and graft potency will expand the scope of cellular therapies. Also the development of adequate ex vivo HSPC expansion strategies could bring expanded cord blood grafts to the forefront of transplant therapy and regenerative medicine.

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