Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Clot-derived contaminants in transplanted bone marrow mononuclear cells impair the therapeutic effect in stroke

Tools
- Tools
+ Tools

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

[img]
Preview
PDF
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

Request Changes to record.

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.

Visual Overview—
An online visual overview is available for this article.

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
Divisions: Faculty of 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: 12 September 2019
Dates:
DateEvent
12 September 2019Published
July 2019Available
Date of first compliant deposit: 7 August 2019
Volume: 50
Number: 10
Page Range: pp. 2883-2891
DOI: 10.1161/STROKEAHA.119.026669
Status: Peer Reviewed
Publication Status: Published
Publisher Statement: 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
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
A79Osaka Universityhttp://dx.doi.org/10.13039/501100004206
01DR17016Bundesministerium für Bildung, Wissenschaft und ForschungUNSPECIFIED

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us