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Integrin α4 overexpression on rat mesenchymal stem cells enhances transmigration and reduces cerebral embolism after intracarotid injection
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Cui, Li-li, Nitzsche, Franziska, Pryazhnikov, Evgeny, Tibeykina, Marina, Tolppanen, Laura, Rytkönen, Jussi, Huhtala, Tuulia, Mu, Jing-wei, Khiroug, Leonard, Boltze, Johannes and Jolkkonen, Jukka (2017) Integrin α4 overexpression on rat mesenchymal stem cells enhances transmigration and reduces cerebral embolism after intracarotid injection. Stroke, 48 (10). pp. 2895-2900. doi:10.1161/STROKEAHA.117.017809 ISSN 0039-2499.
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Official URL: http://dx.doi.org/10.1161/STROKEAHA.117.017809
Abstract
Background and Purpose
Very late antigen-4 (integrin α4β1)/vascular cell adhesion molecule-1 mediates leukocyte trafficking and transendothelial migration after stroke. Mesenchymal stem cells (MSCs) typically express integrin β1 but insufficient ITGA4 (integrin α4), which limits their homing after intravascular transplantation. We tested whether ITGA4 overexpression on MSCs increases cerebral homing after intracarotid transplantation and reduces MSC-borne cerebral embolism.
Methods
Rat MSCs were lentivirally transduced to overexpress ITGA4. In vitro transendothelial migration was assessed using a Boyden chamber assay. Male Wistar rats intracarotidly received 0.5×106 control or modified MSCs 24 hours after sham or stroke surgery. In vivo behavior of MSCs in the cerebral vasculature was observed by intravital microscopy and single-photon emission computed tomography for up to 72 hours.
Results
Transendothelial migration of ITGA4-overexpressing MSCs was increased in vitro. MSCs were passively entrapped in microvessels in vivo and occasionally formed large cell aggregates causing local blood flow interruptions. MSCs were rarely found in perivascular niches or parenchyma at 72 hours post-transplantation, but ITGA4 overexpression significantly decreased cell aggregation and ameliorated the evoked cerebral embolism in stroke rats.
Conclusions
ITGA4 overexpression on MSCs enhances transendothelial migration in vitro, but not in vivo, although it improves safety after intracarotid transplantation into stroke rats.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
| Journal or Publication Title: | Stroke | ||||||||
| Publisher: | Lippincott Williams & Wilkins | ||||||||
| ISSN: | 0039-2499 | ||||||||
| Official Date: | October 2017 | ||||||||
| Dates: |
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| Volume: | 48 | ||||||||
| Number: | 10 | ||||||||
| Page Range: | pp. 2895-2900 | ||||||||
| DOI: | 10.1161/STROKEAHA.117.017809 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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