Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats

Satoshi Kawauchi, Takao Yasuhara, Kyohei Kin, Satoru Yabuno, Chiaki Sugahara, Takayuki Nagase, Kakeru Hosomoto, Yosuke Okazaki, Yousuke Tomita, Michiari Umakoshi, Tatsuya Sasaki, Masahiro Kameda, Cesario V. Borlongan, Isao Date

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. Methods: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. Results: In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. Conclusion: SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell–cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.

Original languageEnglish
JournalCNS Neuroscience and Therapeutics
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • bone marrow stromal cells
  • cerebral infarction
  • encapsulated cell transplantation
  • middle cerebral artery occlusion model
  • neurogenesis

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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