Exosomes from mesenchymal stem cells expressing miR‐125b inhibit neointimal hyperplasia via myosin IE

Abstract

Intercellular communication between mesenchymal stem cells (MSCs) and their target cells in the perivascular environment is modulated by exosomes derived from MSCs. However, the potential role of exosome‐mediated microRNA transfer in neointimal hyperplasia remains to be investigated. To evaluate the effects of MSC‐derived exosomes (MSC‐Exo) on neointimal hyperplasia, their effects upon vascular smooth muscle cell (VSMC) growth in vitro and neointimal hyperplasia in vivo were assessed in a model of balloon‐induced vascular injury. Our results showed that MSC‐Exo were internalised by VSMCs and inhibited proliferation and migration in vitro. Further analysis revealed that miR‐125b was enriched in MSC‐Exo, and repressed the expression of myosin 1E (Myo1e) by targeting its 3ʹ untranslated region. Additionally, MSC‐Exo and exosomally transferred miR‐125b repressed Myo1e expression and suppressed VSMC proliferation and migration and neointimal hyperplasia in vivo. In summary, our findings revealed that MSC‐Exo can transfer miR‐125b to VSMCs and inhibit VSMC proliferation and migration in vitro and neointimal hyperplasia in vivo by repressing Myo1e, indicating that miR‐125b may be a therapeutic target in the treatment of vascular diseases.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges in Clinical Applications

“…They also characterized neural growth factor transcripts in rAMSC-EV (Bucan et al, 2019). Another study from Wang et al (2019) used DIO to label MSC-EV in a rat carotid artery balloon injury model. They found that MSC-EV can transfer miR−125b to vascular smooth muscle cells, which can attenuate neointimal formation and could be a therapeutic target of vascular diseases (Wang et al, 2019).…”

“…Another study from Wang et al (2019) used DIO to label MSC-EV in a rat carotid artery balloon injury model. They found that MSC-EV can transfer miR−125b to vascular smooth muscle cells, which can attenuate neointimal formation and could be a therapeutic target of vascular diseases (Wang et al, 2019). There are also several reports of labeling MSC-EV with different labeling agents such as DiI (1,1 -Dioctadecyl-3,3,3 ,3 -Tetramethylindocarbocyanine Perchlorate), Alexa fluor 488, and gadolinium for locating the biodistribution of EV (Abello et al, 2019;Chew et al, 2019;Cui et al, 2019).…”

Current Knowledge and Future Perspectives on Mesenchymal Stem Cell-Derived Exosomes as a New Therapeutic Agent

“…Tal et al reported that exosomes from miR-126-3p-overexpressing MSCs stimulated angiogenesis and collagen maturity in a diabetic rat model [156]. Exosomes from miR-125b-overexpressing MSCs were reported to repress Myo1e expression and suppress the proliferation and migration of vascular smooth muscle cells in vitro and in vivo, suppressing neointimal hyperplasia [163].…”

Extracellular vesicles therapy: opportunities, mechanisms and perspectives

“…Регенераторный потенциал рассматривается также и при повреждении печени [25][26][27], лёгких [28,29], нервной ткани [30][31][32][33][34][35], кожных покровов [36,37] и микроциркуляторного русла [38]. Перспективными могут оказаться свойства везикул оказывать стимулирующие пролиферацию действия [39][40][41], угнетать воспаление [42][43][44], снижать оксидативный стресс [45].…”

“…Инфаркт миокарда [2][3][4][5][6][7][8][9][10] Крыса [2][3][4][5][6][7]9] По периферии инфаркта [2][3][4] в/в [5][6][7]9] Увеличение фракции выброса [3,5,6], уменьшение КСО ЛЖ [2,5,6] Подавление апоптоза [3-4, 6, 7-9] Индукция ангиогенеза [3][4][5] Уменьшение фиброза [7,9] Альтернативная поляризация макрофагов [7] Усиление АОС [9] Мышь [8,10] Интрамиокардиально [8,10] Подавление апоптоза [8] Уменьшение воспаления, альтернативная активация макрофагов [10] Оксидативный стресс [45] Крыса Инъекция в орган [45] Подавление апоптоза и стимуляция пролиферации [45] Баллон-индуцированное повреждение сосудов [39] Крыса в/в [39] Подавление пролиферации и миграции клеток, уменьшение экспресс...…”