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Review: In vitro generation of red blood cells for transfusion medicine: Progress,prospects and challenges
Authors:Esmond Lee  Jaichandran Sivalingam  Zhong Ri Lim  Gloryn Chia  Low Gin Shi  Mackenna Roberts  Yuin-Han Loh  Shaul Reuveny  Steve Kah-Weng Oh
Institution:1. Stem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Republic of Singapore;2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94305, USA;3. Brilliant Research Pte. Ltd, Singapore 139955, Republic of Singapore;4. Oxford-University College London Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, UK;5. Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research, Singapore 138668, Republic of Singapore;6. Department of Biological Sciences, National University of Singapore, Singapore 117543, Republic of Singapore
Abstract:In vitro generation of red blood cells (RBCs) has the potential to circumvent the shortfalls in global demand for blood for transfusion applications. The conventional approach for RBC generation has been from differentiation of hematopoietic stem cells (HSCs) derived from cord blood, adult bone marrow or peripheral blood. More recently, RBCs have been generated from human induced pluripotent stem cells (hiPSCs) as well as from immortalized adult erythroid progenitors. In this review, we highlight the recent advances to RBC generation from these different approaches and discuss the challenges and new strategies that can potentially make large-scale in vitro generation of RBCs a feasible approach.
Keywords:Red blood cells  Hematopoietic  Induced pluripotent stem cells  Immortalized  Erythroid  Cord blood  2  3 DPG  2  3 diphosphoglcerate  AIDS  Acquired immune deficiency syndrome  ATP  adenosine triphosphate  BM  bone marrow  cRBCs  cultured red blood cells  CB  cord blood  CFSE  carboxyfluorescein succinimidyl ester  EB  embryoid body  FDA  US Food and Drug Administration  G6PDH  Glucose 6-phosphate dehydrogenase  G-CSF  granulocyte colony-stimulating factor  GMP  good manufacturing practise  HBOC  hemoglobin-based oxygen carriers  HbF  fetal hemoglobin  HbA  adult hemoglobin  HSCs  hematopoietic stem cells  hESCs  human embryonic stem cells  hiPSCs  human induced pluripotent stem cells  hPSCs  human pluripotent stem cells  HSPCs  hematopoietic stem and progenitor cells  HiDEP  human iPS cell-derived erythroid progenitor lines  HUDEP  human umbilical cord blood-derived erythroid progenitor lines  iEP  induced erythroid progenitors  imERYPC  immortalized erythrocyte progenitor cell  ImEry  immortalized erythroblast cell line  MCV  mean corpuscular volume  MCH  mean corpuscular hemoglobin  MCHC  mean corpuscular hemoglobin concentration  MSCs  mesenchymal stem cells  PB  peripheral blood  PK  Pyruvate kinase  RBCs  red blood cells
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