Immunomodulation with Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis

Abstract

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.