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In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells

Authors
 Eun Jung Baek  ;  Han-Soo Kim  ;  Sinyoung Kim  ;  Honglien Jin  ;  Tae-Yeal Choi  ;  Hyun Ok Kim 
Citation
 TRANSFUSION, Vol.48(10) : 2235-2245, 2008 
Journal Title
 TRANSFUSION 
ISSN
 0041-1132 
Issue Date
2008
MeSH
Antigens, CD34/metabolism ; Bone Marrow Cells/cytology ; Cell Culture Techniques/methods* ; Coculture Techniques ; Culture Media, Serum-Free/pharmacology ; Erythrocyte Transfusion* ; Erythrocytes/cytology* ; Erythroid Cells/cytology ; Erythropoietin/pharmacology ; Fetal Blood/cytology* ; Humans ; Immunophenotyping ; Interleukin-3/pharmacology ; Mesenchymal Stem Cells/cytology* ; Mesenchymal Stem Cells/metabolism ; Stem Cell Factor/pharmacology ; Stromal Cells/cytology ; Thrombopoietin/pharmacology ; fms-Like Tyrosine Kinase 3/pharmacology
Keywords
Antigens, CD34/metabolism ; Bone Marrow Cells/cytology ; Cell Culture Techniques/methods* ; Coculture Techniques ; Culture Media, Serum-Free/pharmacology ; Erythrocyte Transfusion* ; Erythrocytes/cytology* ; Erythroid Cells/cytology ; Erythropoietin/pharmacology ; Fetal Blood/cytology* ; Humans ; Immunophenotyping ; Interleukin-3/pharmacology ; Mesenchymal Stem Cells/cytology* ; Mesenchymal Stem Cells/metabolism ; Stem Cell Factor/pharmacology ; Stromal Cells/cytology ; Thrombopoietin/pharmacology ; fms-Like Tyrosine Kinase 3/pharmacology
Abstract
BACKGROUND: There is no appropriate alternative source of red blood cells (RBCs) to relieve the worsening shortage of blood available for transfusion. Therefore, in vitro generation of clinically available RBCs from hematopoietic stem cells could be a promising new source to supplement the blood supply. However, there have been few studies about the generation of clinical-grade RBCs by coculture on human mesenchymal stem cells (MSCs) and various cytokine supplements, even though the production of pure RBCs requires coculture on stromal cells and proper cytokine supplements. STUDY DESIGN AND METHODS: Umbilical cord blood (CB) CD34+ cells were cultured in serum-free medium supplemented with two cytokine sets of stem cell factor (SCF) plus interleukin-3 (IL-3) plus erythropoietin (EPO) and SCF plus IL-3 plus EPO plus thrombopoietin (TPO) plus Flt-3 for 1 week, followed by coculture upon MSCs derived from bone marrow (BM) or CB for 2 weeks. RESULTS: Almost pure clinical-grade RBCs could be generated by coculturing with CB-MSCs but not BM-MSCs. Expansion fold and enucleation rate were significantly higher in coculture with CB-MSCs than BM-MSCs. Despite a 2.5-fold expansion of erythroblasts in the presence of TPO and Flt-3 for 8 days, the final RBC count was higher without TPO and Flt-3. CONCLUSIONS: This study is the first report on generating clinical-grade RBCs by in vitro culture with human MSCs and compared effectiveness of several cytokines for RBC production. This provides a useful basis for future production of clinically available RBCs and a model of erythropoiesis that is analogous to the in vivo system
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2008.01828.x/abstract
DOI
18673341
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sin Young(김신영) ORCID logo https://orcid.org/0000-0002-2609-8945
Kim, Han Soo(김한수)
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Baek, Eun Jung(백은정)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107485
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