Immunostimulatory effects of mesenchymal stem cell-derived neurons: Implications for stem cell therapy in allogeneic transplantations

Marianne D. Castillo, Katarzyna A. Trzaska, Steven J. Greco, Nicholas M. Ponzio, Pranela Rameshwar

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Mesenchymal stem cells (MSCs) differentiate along various lineages to specialized mesodermal cells and also transdifferentiate into cells such as ectodermal neurons. MSCs are among the leading adult stem cells for application in regenerative medicine. Advantages include their immune-suppressive properties and reduced ethical concerns. MSCs also show immune-enhancing functions. Major histocompatibility complex II (MHC-II) is expected to be downregulated in MSCs during neurogenesis. Ideally, "off the shelf"MSCs would be suited for rapid delivery into patients. The question is whether these MSC-derived neurons can reexpress MHC-II in a milieu of inflammation. Western analyses demonstrated gradual decrease in MHC-II during neurogenesis, which correlated with the expression of nuclear CIITA, the master regulator of MHC-II expression. MHC-II expression was reversed by exogenous IFNYγ. One-way mixed lymphocyte reaction with partly differentiated neurons showed a stimulatory effect, which was partly explained by the release of the proinflammatory neurotransmitter substance P (SP), cytokines, and decreases in miR-130a and miR-206. The anti-inflammatory neurotransmitters VIP and CGRP were decreased at the peak time of immune stimulation. In summary, MSC-derived neurons show decreased MHC-II expression, which could be reexpressed by IFNY. The release of neurotransmitters could be involved in initiating inflammation, underscoring the relevance of immune responses as consideration for stem cell therapies.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalClinical and translational science
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2008

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Keywords

  • CIITA
  • Cytokines
  • IFN<inf>γ</inf>
  • Immune response
  • MHC-II
  • MicroRNA
  • Neural repair
  • Stem cells

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