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Platelet‐derived growth factor promotes ex vivo expansion of CD34 + cells from human cord blood and enhances long‐term culture‐initiating cells, non‐obese diabetic/severe combined immunodeficient repopulating cells and formation of adherent cells
Author(s) -
Su Rui Jun,
Zhang Xiao Bing,
Li Karen,
Yang Mo,
Li Chi Kong,
Fok Tai Fai,
James Anthony Edward,
Pong Henry,
Yuen Patrick Man Pan
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03500.x
Subject(s) - progenitor cell , cd34 , cord blood , stem cell factor , stem cell , platelet derived growth factor receptor , biology , growth factor , interleukin 3 , ex vivo , cytokine , cd38 , microbiology and biotechnology , immunology , cancer research , medicine , antigen presenting cell , in vivo , t cell , receptor , immune system
Summary. Platelet‐derived growth factor (PDGF) is a major mitogen for connective tissue cells. In this study, we investigated the effects and mechanism of PDGF on the ex vivo expansion of cord blood CD34 + cells. Our data demonstrated that among various cytokine combinations of thrombopoietin (TPO), interleukin 1 beta (IL‐1β), IL‐3, IL‐6 and Flt‐3 ligand (Flt‐3L), TPO + IL‐6 + Flt‐3L was most efficient in promoting the expansion of CD34 + cells, CD34 + CD38 – cells, mixed‐lineage colony‐forming units (CFU‐GEMM) and long‐term culture‐initiating cells (LTC‐IC) by 21·7 ± 5·00‐, 103 ± 27·9‐, 10·7 ± 7·94‐ and 6·52 ± 1·51‐fold, respectively, after 12–14 d of culture. The addition of PDGF increased the yield of these early progenitors by 45·0%, 66·5%, 45·1% and 79·8% respectively. More significantly, PDGF enhanced the engraftment of human CD45 + cells and their myeloid subsets (CD33 + , CD14 + cells) in non‐obese diabetic (NOD)/severe‐combined immunodeficient (SCID) mice. The expression of PDGF receptor (PDGFR)‐β was not detectable in fresh CD34 + cells but was upregulated after culture for 3 d. PDGF also enhanced the development of adherent cells/clusters that expressed the endothelial markers VE‐cadherin and CD31. These findings suggest that PDGF is an effective cytokine for the ex vivo expansion of early stem and progenitor cells. The mechanism could be mediated by PDGFR‐β on committed CD34 + progenitor cells and/or secondary to the stimulation of autologous, stromal feeder cells.