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Bone marrow mononuclear cells activate angiogenesis via gap junction mediated cell-cell interaction
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Kikuchi-Taura, Akie , Okinaka, Yuka, Takeuchi, Yukiko, Ogawa, Yuko, Maeda, Mitsuyo, Kataoka, Yosky, Yasui, Teruhito, Kimura, Takafumi, Gul, Sheraz, Claussen, Carsten, Boltze, Johannes and Taguchi, Akihiko (2020) Bone marrow mononuclear cells activate angiogenesis via gap junction mediated cell-cell interaction. Stroke, 51 (4). pp. 1279-1289. doi:10.1161/STROKEAHA.119.028072 ISSN 0039-2499.
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Official URL: https://doi.org/10.1161/STROKEAHA.119.028072
Abstract
Background and Purpose—
Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis.
Methods—
We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue.
Results—
The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed.
Conclusions—
Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QM Human anatomy Q Science > QP Physiology |
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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 cells, Blood-vessels -- Growth, Cell interaction | ||||||||
| Journal or Publication Title: | Stroke | ||||||||
| Publisher: | Lippincott Williams & Wilkins | ||||||||
| ISSN: | 0039-2499 | ||||||||
| Official Date: | April 2020 | ||||||||
| Dates: |
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| Volume: | 51 | ||||||||
| Number: | 4 | ||||||||
| Page Range: | pp. 1279-1289 | ||||||||
| DOI: | 10.1161/STROKEAHA.119.028072 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Copyright Holders: | © 2020 American Heart Association, Inc. | ||||||||
| Date of first compliant deposit: | 31 January 2020 | ||||||||
| Date of first compliant Open Access: | 19 August 2020 | ||||||||
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