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
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.