Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion

Haiyan Xu, Kazunori Miki, Satoru Ishibashi, Jun Inoue, Liyuan Sun, Shu Endo, Ichiro Sekiya, Takeshi Muneta, Joji Inazawa, Mari Dezawa, Hidehiro Mizusawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The options for treating stroke are limited, but stem cells hold promise as a therapy because of their multipotency. Neuronal cells derived from mesenchymal stem cells (MSC) were reported to have more therapeutic effect than MSCs. For elucidating the therapeutic mechanism of neuronal cells, here we generated a model of focal cerebral infarction by performing left common carotid artery occlusion in adult gerbils. We transfected human trabecular bone-derived MSCs (hMSCs) with the Notch intracellular domain to induce their differentiation into neuronal cells (hN-MSCs). These cells were stereotaxically transplanted into the local ischemic hemisphere 4 days after the occlusion. Behavioral analyses were conducted 28 days after transplantation, and then fluorescence in situ hybridization (FISH) and a histological evaluation were performed. Histologically, transplanted cells were distributed around the periinfarct region, and approximately 8.5% and 4.2% of hN-MSCs and hMSCs survived, respectively; 53.2% ± 9.6% of hN-MSCs were microtubule-associated protein 2+ (MAP-2+) and extended neurites, whereas only 0.9% ± 0.3% of hMSCs were MAP-2+. In FISH, human nucleus-specific signals were detected in both hN-MSCs and hMSCs grafted brains, but no transplanted cell had a merged gerbil-specific nuclear signals. hN-MSC-transplanted animals showed significantly better recovery than animals given control vehicle in the T-maze, bilateral asymmetry, and open field tests. These findings suggested that hN-MSCs have greater therapeutic potential than hMSCs for stroke and that cell fusion does not primarily contribute to the therapeutic mechanism of MSC transplantation.

Original languageEnglish
Pages (from-to)3598-3609
Number of pages12
JournalJournal of Neuroscience Research
Volume88
Issue number16
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • Cell fusion
  • Focal ischemia
  • Functional recovery
  • Mesenchymal stem cell
  • Neuronal cell

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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