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

Maple L. Shiao; Ce Yuan; Andrew T. Crane; Joseph P. Voth; Mario Juliano; Laura L. Hocum Stone; Zhenghong Nan; Ying Zhang; Nicole Kuzmin-Nichols; Paul R. Sanberg; Andrew W. Grande; Walter C. Low

doi:10.1177/0963689719836763

Cell Transplantation (Jul 2019)

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

Maple L. Shiao,
Ce Yuan,
Andrew T. Crane,
Joseph P. Voth,
Mario Juliano,
Laura L. Hocum Stone,
Zhenghong Nan,
Ying Zhang,
Nicole Kuzmin-Nichols,
Paul R. Sanberg,
Andrew W. Grande,
Walter C. Low

Affiliations

Maple L. Shiao: Both the authors are co-first authors in this article.
Ce Yuan: Both the authors are co-first authors in this article.
Andrew T. Crane: Department of Neurosurgery, University of Minnesota, Minneapolis, USA
Joseph P. Voth: Department of Neurosurgery, University of Minnesota, Minneapolis, USA
Mario Juliano: Department of Neurosurgery, University of Minnesota, Minneapolis, USA
Laura L. Hocum Stone: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, USA
Zhenghong Nan: Department of Neurosurgery, University of Minnesota, Minneapolis, USA
Ying Zhang: Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, USA
Nicole Kuzmin-Nichols: Saneron CCEL Therapeutics Inc, Tampa, USA
Paul R. Sanberg: Center for Brain Repair and Department of Neurosurgery, Morsani College of Medicine, University of South Florida, Tampa, USA
Andrew W. Grande: Both the authors are co-senior authors of this article.
Walter C. Low: Both the authors are co-senior authors of this article.

DOI: https://doi.org/10.1177/0963689719836763
Journal volume & issue: Vol. 28

Abstract

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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.

Published in Cell Transplantation

ISSN: 0963-6897 (Print); 1555-3892 (Online)
Publisher: SAGE Publishing
Country of publisher: United States
LCC subjects: Medicine
Website: http://journals.sagepub.com/home/cll

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