TY - JOUR
T1 - Mechanistic Basis of ex Vivo Umbilical Cord Blood Stem Progenitor Cell Expansion
AU - Sica, R. Alejandro
AU - Terzioglu, Meryem K.
AU - Mahmud, Dolores
AU - Mahmud, Nadim
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Blood cell
KW - Bone marrow
KW - Epigenetic
KW - Expansion
KW - Graft
KW - Transplantation
KW - Umbilical cord blood
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U2 - 10.1007/s12015-020-09981-w
DO - 10.1007/s12015-020-09981-w
M3 - Review article
C2 - 32424674
AN - SCOPUS:85085584168
SN - 2629-3269
VL - 16
SP - 628
EP - 638
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 4
ER -