Immune effects of mesenchymal stromal cells in experimental stroke

Franziska Scheibe, Juliane Ladhoff, Jojanneke Huck, Maik Grohmann, Katja Blazej, Arif Oersal, Nevena Baeva, Martina Seifert, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

Preclinical trials confirmed the potential of mesenchymal stromal cells (MSCs) to improve functional recovery after experimental stroke. Beneficial effects of MSCs are often attributed to their immunosuppressive/immunomodulatory functions. Surprisingly, the influence of MSCs on the immune system after stroke is poorly understood, but requires special consideration because cerebral ischemia is associated with stroke-induced immunodepression that predisposes to bacterial infections with increased mortality. In this study, we intravenously transplanted syngeneic murine bone marrow-derived MSCs (mMSCs) into C57BL/6 mice at 6 hours after transient middle cerebral artery occlusion (MCAo; 60 minutes) to investigate the impact of MSCs on stroke-induced immunodepression. Transplantation of syngeneic splenocytes or phosphate-buffered saline (PBS) served as controls. An immune status was determined by flow cytometry on days 3 and 14 after MCAo, which did not reveal any negative effects of cell transplantation on stroke-induced immunodepression. Although our mMSCs were found to exert immunosuppressive effects in vitro, stroke-mediated immune cell dysfunction was not altered by mMSCs in ex-vivo stimulation assays with lipopolysaccharide or concanavalin A. Moreover, systemic inflammatory cytokine levels (interleukin-6, tumor necrosis factorα, interferonγ, monocyte chemoattractant protein-1) remained unchanged in the sera of mice after cerebral ischemia and cell transplantation. These results reduce safety concerns about MSC administration in ongoing clinical stroke trials.

Original languageEnglish
Pages (from-to)1578-88
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number8
DOIs
Publication statusE-pub ahead of print - 2 May 2012

Keywords

  • Animals
  • Cell Culture Techniques
  • Cell Proliferation
  • Cytokines
  • Disease Models, Animal
  • Flow Cytometry
  • Immune Tolerance
  • Injections, Intravenous
  • Leukocyte Count
  • Leukocytes, Mononuclear
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Inbred C57BL
  • Spleen
  • Stroke
  • Transplantation Immunology
  • Journal Article
  • Research Support, Non-U.S. Gov't

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