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TNFa Antagonizes PDGF‐AB Chemotactic Effects on Mesenchymal Stem Cells (MSC) Migration
Author(s) -
Phua Andy Yong Han,
Vijayakumar Praveen,
Choolani Mahesh,
Chan Jerry,
Lim YawChyn
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb354
Subject(s) - platelet derived growth factor receptor , mesenchymal stem cell , chemokine , cell migration , chemotaxis , cytokine , chemistry , microbiology and biotechnology , tumor necrosis factor alpha , in vitro , growth factor , platelet derived growth factor , immunology , biology , inflammation , biochemistry , receptor
MSC are a promising cell source for cellular therapy but often, systemic delivery to target tissues is sub‐optimal. Aim: This study examines the effects of pro‐ and anti‐inflammatory mediators and growth factors on MSC migration in vitro. Methods The effects of various chemokines/cytokines, growth factors and lipid mediators (used alone or in combinations) on MSC migration was determined using transwell assays. After 5hr of incubation, the inserts were fixed and stained with Giemsa stain. 21 random fields were digitized at 100x magnification and the mean number of transmigrated cells/field determined. Result Compared to media control (14±5 cells), MSC migration was significantly increased in the presence of PDGF‐AB (59±21 cells) and IGF‐1 (28±13 cells) whereas SDF‐1, bFGF, SLC, GM‐CSF, VEGF, LTB4 and LXA4 had no detectable chemotactic effect. We found that TNFa significantly inhibited MSC migration (7±2 cells). Furthermore, the addition of TNFa together with PDGF‐AB into the bottom well also significantly inhibited the PDGF‐AB induced migration by 41.3±11.3% (p<0.05 as compared to PDGF‐AB alone). Conclusion TNFa significantly inhibits both baseline and PDGF‐AB induced MSC migration in‐vitro. Our data suggest that the precise composition of the cytokine/chemokine milieu at the injury site will greatly influence MSC recruitment into the tissue. This research is funded by URC NUS.