open access

https://hdl.handle.net/2115/70801

Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct

Optimal timing/dose of cell therapy

英語

transplantation

2013-04

Wiley

Neuropathology

33(2)

140-148

Objective: Stereotactic transplantation of bone marrow stromal cells (BMSCs) enables efficient delivery to the infarct brain. This study was aimed to assess its optimal timing and cell dose for ischemic stroke. Methods: The BMSCs were harvested from the GFP-transgenic rats and were labeled with quantum dots. The BMSCs (1 x 10^5 or 1 x 10^6) were stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion at 1 or 4 weeks post-ischemia. Motor function was serially assessed. Using in vivo near infrared (NIR) fluorescence imaging, the engrafted BMSCs were visualized at 3 weeks post-transplantation. Immunohistochemistry was performed to evaluate their fate. Results: Functional recovery was significantly enhanced when both low and high doses of BMSCs were transplanted at 1 week post-ischemia, but such therapeutic effects was observed only when the high-dose BMSCs were transplanted at 4 weeks post-ischemia. Both optical imaging and immunohistochemistry revealed their better engraftment in the peri-infarct area when the high-dose BMSCs were transplanted at 1 or 4 weeks post-ischemia. Conclusion: These findings strongly suggest the importance of timing and cell dose to yield therapeutic effects of BMSC transplantation for ischemic stroke. Earlier transplantation requires a smaller number of donor cells for beneficial effects.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Kawabori, M., Kuroda, S., Ito, M., Shichinohe, H., Houkin, K., Kuge, Y. and Tamaki, N. (2013), Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct. Neuropathology, 33: 140-148., which has been published in final form at https://doi.org/10.1111/j.1440-1789.2012.01335.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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