Stem cell expansion - Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood

Citation
Rj. Su et al., Stem cell expansion - Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood, BONE MAR TR, 27(10), 2001, pp. 1075-1080
Citations number
33
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Journal title
BONE MARROW TRANSPLANTATION
ISSN journal
02683369 → ACNP
Volume
27
Issue
10
Year of publication
2001
Pages
1075 - 1080
Database
ISI
SICI code
0268-3369(200105)27:10<1075:SCE-PG>2.0.ZU;2-#
Abstract
Infusion of ex vivo expanded megakaryocytic (MK) progenitor cells is a stra tegy for shortening the duration of thrombocytopenia after haematopoietic s tem cell transplantation. The cell dose after expansion has emerged as a cr itical factor for achieving the desired clinical outcomes. This study aimed to establish efficient conditions for the expansion of the MK lineage from enriched CD34(+) cells of umbilical cord blood and to investigate the effe ct of platelet-derived growth factor (PDGF) in this system. Our results dem onstrated that thrombopoietin (TPO) alone produced a high proportion of CD6 1(+)CD41(+) cells but a low total cell count and high cell death, resulting in an inferior expansion. The addition of interleukin-1 beta (IL-1 beta), Flt-3 ligand (Flt-3L) and to a lesser extent IL-3 improved the expansion ou tcome. The treatment groups with three to five cytokines produced efficient expansions of CFU-MK up to 400-fold with the highest yield observed in the presence of TPO, IL-1 beta, IL-3, IL-6 and Flt-3L, CD34(+) cells were expa nded by five to 22-fold. PDGF improved the expansion of all cell types with CD61(+)CD41(+) cells, CFU-MK and CD34(+) cells increased by 101%, 134% and 70%, respectively. On day 14, the CD61(+) population consisted of diploid (86.5%), tetraploid (11.8%) and polyploid (8N-32N; 1.69%) cells. Their leve ls were not affected by PDGF, TPO, IL-1 beta, 1L-3, IL-6, Flt-3L and PDGF r epresented an effective cytokine combination for expanding MK progenitors w hile maintaining a moderate increase of CD34(+) cells. This study showed, f or the first time, that PDGF enhanced the ex vivo expansion of the MK linea ge, without promoting their in vitro maturation. PDGF might be a suitable g rowth factor to improve the ex vivo expansion of MK progenitors for clinica l applications.