Neuronal apoptosis is inhibited by cord blood stem cells after spinal cord injury.
Spinal cord injury (SCI) induces a series of endogenous biochemical changes that lead to secondary damage involving apoptosis as one of the major events. To understand the molecular basis of apoptosis after spinal cord injury, we subjected male rats to spinal cord injury using a weight drop device (NYU impactor) and evaluated the therapeutic potential of human umbilical cord blood stem cells (hUCB), which were stereotactically transplanted into the injury epicenter 1 week after SCI. We identified genes that render the adult-injured spinal cord nonconducive and the hUCB-treated spinal cord conducive to regeneration and repair at 3 weeks post-injury using an RT-PCR microarray by analyzing 84 apoptotic genes. Genes involved in inflammation and apoptosis were upregulated in injured spinal cords of rats, whereas genes involved in neuroprotection were upregulated in the hUCB-treated rats. Quantitative RT-PCR verified mRNA changes in the apoptotic genes of TNF-alpha, TNFR1, TNFR2, Fas, Lta, and CD40. Based on these results, we evaluated the role of TNF-alpha and its related apoptotic genes in neuronal death after SCI. Changes in the expression of TNF-alpha, TNFR1, and TNFR2 were observed over a period of 3 weeks post-SCI and after treatment with hUCB. Expression of P50 and P65 on neurons after SCI was efficiently downregulated by hUCB. These results were confirmed by the evaluation of apoptotic proteins of co-cultures of spinal neurons with hUCB under in-vitro conditions. The results of this study suggest that hUCB have therapeutic potential in inhibiting neuronal apoptosis during the repair of injured spinal cord.
Dasari
Venkata Ramesh
VR
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61656, USA.
Veeravalli
Krishna Kumar
KK
Tsung
Andrew J
AJ
Gondi
Christopher S
CS
Gujrati
Meena
M
Dinh
Dzung H
DH
Rao
Jasti S
JS
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000601:surgery*