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

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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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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing. We would also like to thank James Zacny, PhD, for his critical review of the manuscript and his helpful suggestions. We also acknowledge contributions of Amudha Ganapathy, PhD and Benjamin Petro for their asistance with literature search and technical review of the draft manuscript.

Funding

The studies reported in this review from the Mahmud laboratory were supported in part by the Leukemia Lymphoma Society Translational Research Program, the University of Illinois at Chicago Chancellor’s Innovation Award, and Office of Vice Chancellor for Research Areas of Excellence Award to Dr. Nadim Mahmud. The funders had no role in study design, data collection and analysis, or preparation of the manuscript.

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  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

    R. Alejandro Sica, Meryem K. Terzioglu, Dolores Mahmud & Nadim Mahmud

  2. University of Illinois Cancer Center, Chicago, IL, USA

    Nadim Mahmud

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  1. R. Alejandro Sica
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Sica, R.A., Terzioglu, M.K., Mahmud, D. et al. Mechanistic Basis of ex Vivo Umbilical Cord Blood Stem Progenitor Cell Expansion. Stem Cell Rev and Rep 16, 628–638 (2020). https://doi.org/10.1007/s12015-020-09981-w

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