Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model

Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenes...

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Bibliographic Details
Published in:Scientific reports 2021-01, Vol.11 (1), p.2543-2543, Article 2543
Main Authors: Maeda, Shusaku, Miyagawa, Shigeru, Kawamura, Takuji, Shibuya, Takashi, Watanabe, Kenichi, Nakagawa, Takaya, Harada, Akima, Chida, Dai, Sawa, Yoshiki
Format: Article
Language:English
Subjects:
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692/4019
Adductor muscle
Angiogenesis
Arterioles
Cell therapy
Endothelial cells
Femoral artery
Gene expression
Humanities and Social Sciences
Ischemia
Mesenchymal stem cells
multidisciplinary
Perfusion
Science
Science (multidisciplinary)
Signal transduction
Stem cell transplantation
Stem cells
Transcriptomes
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Summary:Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 10 5 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter  > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-82284-3