Treatment with adipose-derived regenerative cells enhances ischemia-induced angiogenesis via exosomal microRNA delivery in mice

Posted: 2021-09-23 19:00:00
Adipose-derived regenerative cells (ADRCs), mesenchymal stem/progenitor cells from subcutaneous adipose tissue, have been shown to stimulate angiogenesis in hind limb ischemia, an effect attributed to paracrine action on endothelial cells (ECs) in mice. Despite promising therapeutic effects, the relevant molecules promoting neovascularization in this setting have not been fully elucidated. Extracellular vesicles, crucial mediators of intercellular communication, are recognized as a new therapeutic modality for regenerative medicine. Here, we found that GW4869, an exosome biogenesis inhibitor targeting neutral sphingomyelinase, impaired ADRCs-mediated angiogenesis and improvement of blood perfusion in a murine hind limb ischemia model. In addition, while the supernatant of ADRCs induced murine EC migration, this effect was attenuated by pre-treatment with GW4869. RNA analysis revealed that treatment of ADRCs with GW4869 reduced the expression of microRNA-21 (miR-21), miR-27b, miR-322, and let-7i in ADRCs-derived exosomes. Furthermore, the exosomes derived from GW4869-treated ADRCs induced the expression of the miR-21 targets Smad7 and Pten, and the miR-322 target Cul2, in ECs. These findings suggest that several miRNAs in ADRCs-derived exosomes contribute to angiogenesis and improvement of blood perfusion in a murine hind limb ischemia model. Keywords: adipose-derived regenerative cells (ADRCs); circulating microRNA; hind limb ischemia; therapeutic angiogenesis.

参考サイト PubMed: exsome

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9月 18, 2019 バイオアソシエイツ


健康な心筋組織を保護することで損傷を減らす心臓発作の直後に服用できる薬があると想像して欲しい。 心臓発作が起きた場合、心臓の専門医は、「時は筋肉なり」と言うと、バージニア工科大学カリリオン心臓医療センター・フラリン生物医学研究所のディレクターであるRobert Gourdie博士(写真)は語った。 血流によって酸素が供給されないと、心臓細胞はすぐに死ぬ。…

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