Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation.

Sudipto Bari, Kevin Kwee Hong Seah, Zhiyong Poon, Alice Man Sze Cheung, Xiubo Fan, Shin-Yeu Ong, Shang Li, Liang Piu Koh, William Ying Khee Hwang

Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2016;21(6):1008-19

PMID: 25555449

Abstract

The successful expansion of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB) for transplantation could revolutionize clinical practice by improving transplantation-related outcomes and making available UCB units that have suboptimal cell doses for transplantation. New cytokine combinations appear able to promote HSPC growth with minimal differentiation into mature precursors and new agents, such as insulin-like growth factor-binding protein 2, are being used in clinical trials. Molecules that simulate the HSPC niche, such as Notch ligand, have also shown promise. Further improvements have been made with the use of mesenchymal stromal cells, which have made possible UCB expansion without a potentially deleterious prior CD34/CD133 cell selection step. Chemical molecules, such as copper chelators, nicotinamide, and aryl hydrocarbon antagonists, have shown excellent outcomes in clinical studies. The use of bioreactors could further add to HSPC studies in future. Drugs that could improve HSPC homing also appear to have potential in improving engraftment times in UCB transplantation. Technologies to expand HSPC from UCB and to enhance the homing of these cells appear to have attained the goal of accelerating hematopoietic recovery. Further discoveries and clinical studies are likely to make the goal of true HSPC expansion a reality for many applications in future.

Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Address: Department of Hematology, Singapore General Hospital, Singapore; Department of Pharmacy, National University of Singapore, Singapore.; Sydney Medical School, The University of Sydney, Australia.; BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, Singapore.; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.; Department of Clinical Research, Singapore General Hospital, Singapore.; Department of Hematology, Singapore General Hospital, Singapore.; Department of Hematology-Oncology, National University Cancer Institute, Singapore.; Department of Hematology, Singapore General Hospital, Singapore; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore; Singapore Cord Blood Bank, Singapore. Electronic address: [email protected].
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