The treatment of TBI with human marrow stromal cells impregnated into collagen scaffold: functional outcome and gene expression profile.
We have previously demonstrated that human marrow stromal cells (hMSCs) embedded in collagen I scaffolds significantly enhance the restorative therapeutic effect of hMSCs after traumatic brain injury (TBI). In this study, we test the hypothesis that the collagen scaffold alters gene expression in hMSCs and that hMSCs impregnated into scaffolds increase the astrocytic expression of vascular endothelial growth factor (VEGF) in the injured brain. Following TBI induced by controlled cortical impact injury, scaffold with hMSCs (3.0×10(6)), hMSCs-only and saline were implanted into the lesion cavity one week after brain injury (n=8/each group). Morris water maze and modified neurological severity scores were performed to evaluate the spatial learning and sensorimotor functions, respectively. Lesion volume and expression of VEGF were measured one week after different treatments. In vitro, total RNA from hMSCs was extracted one week after culture with or without collagen I scaffold for evaluation of gene microarrays. Furthermore, an RT-PCR study on a select subgroup of genes was performed to identify the changes of expression between the culturing hMSCs with collagen scaffolds and hMSCs only. The treatment of TBI with collagen scaffold impregnated with hMSCs significantly decreases the functional deficits from TBI within 7days after treatment, and significantly enhances the VEGF expression of astrocytes in the injured brain compared to the hMSCs-only group. In vitro data indicate that collagen scaffolds stimulate hMSCs to express multiple factors which may contribute to hMSC survival, tissue repair and functional recovery after TBI.
Department of Neurosurgery of Henry Ford Hospital, Detroit, MI, USA.
Changsheng
C
Qu
Asim
A
Mahmood
Xian Shuang
XS
Liu
Ye
Y
Xiong
Lei
L
Wang
Hongtao
H
Wu
Bo
B
Li
Zheng Gang
ZG
Zhang
David L
DL
Kaplan
Michael
M
Chopp
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001930:Brain Injuries / Q000601:surgery*; D002454:Cell Differentiation; D003094:Collagen; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D018782:Maze Learning; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000637:transplantation*; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D009419:Nerve Tissue Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003094:Collagen