Additive behavioral improvement after combined cell therapy and rehabilitation despite long-term microglia presence in stroke rats

Abdulhameed Bakreen, Miia Juntunen, Yannick Dunlop, Irene F. Ugidos, Tarja Malm, Susanna Miettinen, Jukka Jolkkonen

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Microglia are involved in the post-stroke immunomodulation of brain plasticity, repair, and reorganization. Here, we evaluated whether adipose-tissue-derived mesenchymal stem cells (ADMSCs) and/or rehabilitation improve behavioral recovery by modulating long-term perilesional inflammation and creating a recovery-permissive environment in a rat model of ischemic stroke. Methods: A two-way mixed lymphocyte reaction was used to assess the immunomodulatory capacity of ADMSCs in vitro. Two or 7 days after permanent middle cerebral artery occlusion (pMCAO), rats were intravenously administered ADMSCs or vehicle and housed in a standard or enriched environment (EE). Behavioral performance was assessed with a cylinder test, then we performed stereological and ImageJ/Fiji quantifications of ionized calcium-binding adaptor molecule 1 (Iba1) cells and blood–brain barrier (BBB) leakage. Results: Human ADMSCs were immunosuppressive in vitro. The cylinder test showed partial spontaneous behavioral recovery of pMCAO rats, which was further improved by combined ADMSCs and housing in EE on days 21 and 42 (p < 0.05). We detected an ischemia-induced increase in numbers, staining intensity, and branch length of Iba1+ microglia/macrophages as well as BBB leakage in the perilesional cortex. However, these were not different among pMCAO groups. Conclusion: Combined cell therapy and rehabilitation additively improved behavioral outcome despite long-term perilesional microglia presence in stroke rats.

Original languageEnglish
Article number1512
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - 3 Feb 2021
Publication typeA1 Journal article-refereed


  • Blood–brain barrier
  • Cell therapy
  • Inflammation
  • Microglia
  • Rehabilitation
  • Reorganization
  • Repair
  • Spontaneous recovery
  • Stroke

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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