This work was supported by the Korea Research Foundation (Grant KRF-2007-313-E00445) funded by the Korean government (MOEHRD).
In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells
Article first published online: 31 JUL 2008
© 2008 American Association of Blood Banks
Volume 48, Issue 10, pages 2235–2245, October 2008
How to Cite
Baek, E. J., Kim, H.-S., Kim, S., Jin, H., Choi, T.-Y. and Kim, H. O. (2008), In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells. Transfusion, 48: 2235–2245. doi: 10.1111/j.1537-2995.2008.01828.x
- Issue published online: 1 OCT 2008
- Article first published online: 31 JUL 2008
- Received for publication January 23, 2008; revision received April 22, 2008; and accepted April 28, 2008.
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.