Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: growth factor production.
Treatment of traumatic brain injury (TBI) with bone marrow stromal cells (MSCs) improves functional outcome in the rat. However, the specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Currently, the ability of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue appears limited at best. Tissue replacement, however, is not the only possible compensatory avenue in cell transplantation therapy. Various growth factors have been shown to mediate the repair and replacement of damaged tissue, so trophic support provided by transplanted MSCs may play a role in the treatment of damaged tissue. We therefore investigated the temporal profile of various growth factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of rat brain in vitro and quantitative sandwich enzyme-linked immunosorbent assays (ELISAs) were performed. TBI-conditioned hMSCs cultures demonstrated a time-dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive production of these growth factors by the hMSCs. The ELISA data suggest that transplanted hMSCs may provide therapeutic benefit via a responsive secretion of an array of growth factors that can foster neuroprotection and angiogenesis.
Chen
Xiaoguang
X
Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Katakowski
Mark
M
Li
Yi
Y
Lu
Dunyue
D
Wang
Lei
L
Zhang
Lijie
L
Chen
Jieli
J
Xu
Yongxian
Y
Gautam
Subhash
S
Mahmood
Asim
A
Chopp
Michael
M
D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D001930:Brain Injuries / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D014020:Tissue Extracts / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D019208:Brain-Derived Neurotrophic Factor; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D014020:Tissue Extracts; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D020932:Nerve Growth Factor