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Clot-derived contaminants in transplanted bone marrow mononuclear cells impair the therapeutic effect in stroke
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Okinaka, Yuka, Kikuchi-Taura, Akie, Takeuchi, Yukiko, Ogawa, Yuko, Boltze, Johannes, Gul, Sheraz, Claussen, Carsten and Taguchi, Akihiko (2019) Clot-derived contaminants in transplanted bone marrow mononuclear cells impair the therapeutic effect in stroke. Stroke, 50 (10). pp. 2883-2891. doi:10.1161/STROKEAHA.119.026669 ISSN 0039-2499.
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WRAP-clot-derived-contaminants-transplanted-bone-marrow-mononuclear-cells-impair-therapeutic-effect-stroke-Boltze-2019.pdf - Accepted Version - Requires a PDF viewer. Download (1039Kb) | Preview |
Official URL: https://doi.org/10.1161/STROKEAHA.119.026669
Abstract
Background and Purpose—
The beneficial effects of bone marrow mononuclear cell (BM-MNC) transplantation in preclinical experimental stroke have been reliably demonstrated. However, only overall modest effects in clinical trials were observed. We have investigated and reported a cause of the discrepancy between the preclinical and clinical studies.
Methods—
To investigate the possible cause of low efficacy of BM-MNC transplantation in experimental stroke, we have focused on blood clot formation, which is not uncommon in human bone marrow aspirates. To evaluate the effects of clot-derived contaminants in transplanted BM-MNC on stroke outcome, a murine stroke model was used.
Results—
We show that BM-MNC separated by an automatic cell isolator (Sepax2), which does not have the ability to remove clots, did not attenuate brain atrophy after stroke. In contrast, manually isolated, clot-free BM-MNC exerted therapeutic effects. Clot-derived contaminants were also transplanted intravenously to poststroke mice. We found that the transplanted contaminants were trapped at the peristroke area, which were associated with microglial/macrophage activation.
Conclusions—
Clot-derived contaminants in transplanted BM-MNC nullify therapeutic effects in experimental stroke. This may explain neutral results in clinical trials, especially in those using automated stem cell separators that lack the ability to remove clot-derived contaminants.
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| Item Type: | Journal Article | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| Library of Congress Subject Headings (LCSH): | Bone marrow, Bone marrow -- Transplantation -- Complications, Stem cells, Stem cells -- Transplantation, Cerebrovascular disease, Cerebrovascular disease -- Diagnosis, Hematopoietic stem cells, Monocytes, Cellular therapy, Cytology | |||||||||
| Journal or Publication Title: | Stroke | |||||||||
| Publisher: | Lippincott Williams & Wilkins | |||||||||
| ISSN: | 0039-2499 | |||||||||
| Official Date: | October 2019 | |||||||||
| Dates: |
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| Volume: | 50 | |||||||||
| Number: | 10 | |||||||||
| Page Range: | pp. 2883-2891 | |||||||||
| DOI: | 10.1161/STROKEAHA.119.026669 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Reuse Statement (publisher, data, author rights): | This is a non-final version of an article published in final form in Okinaka, Yuka, Kikuchi-Taura, Akie, Takeuchi, Yukiko, Ogawa, Yuko, Boltze, Johannes, Gul, Sheraz, Claussen, Carsten and Taguchi, Akihiko (2019) Clot-derived contaminants in transplanted bone marrow mononuclear cells impair the therapeutic effect in stroke. Stroke, 50 (10). pp. 2883-2891. doi:10.1161/STROKEAHA.119.026669 | |||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||
| Date of first compliant deposit: | 7 August 2019 | |||||||||
| Date of first compliant Open Access: | 12 March 2020 | |||||||||
| RIOXX Funder/Project Grant: |
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