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

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Title: Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct
Other Titles: Optimal timing/dose of cell therapy
Authors: Kawabori, Masahito Browse this author →KAKEN DB
Kuroda, Satoshi Browse this author →KAKEN DB
Ito, Masaki Browse this author
Shichinohe, Hideo Browse this author →KAKEN DB
Houkin, Kiyohiro Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Tamaki, Nagara Browse this author →KAKEN DB
Keywords: Bone marrow stromal cell
cerebral infarct
timing
dose
transplantation
Issue Date: Apr-2013
Publisher: Wiley
Journal Title: Neuropathology
Volume: 33
Issue: 2
Start Page: 140
End Page: 148
Publisher DOI: 10.1111/j.1440-1789.2012.01335.x
PMID: 22725254
Abstract: 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.
Rights: 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.
Type: article (author version)
URI: http://hdl.handle.net/2115/70801
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 川堀 真人

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