microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential

Qiao, Li; Hu, Shiqi; Liu, Suyun; Zhang, Hui; Ma, Hong; Huang, Ke; Li, Zhenhua; Su, Teng; Vandergriff, Adam C.; Tang, Junnan; Allen, Tyler A.; Dinh, Phuong‐Uyen; Cores, Jhon; Yin, Qi; Li, Yongjun

doi:10.1172/jci123135

Cited by 211 publications

(177 citation statements)

References 56 publications

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“…Exosomes contain abundant miRNAs to regulate the expression of related genes in receptor cells and promote the regeneration and repair of receptor cells. It has been reported that exosomal miR-32-5p induced multidrug resistance by inhibited PTEN expression and activates the PI3K/AKT pathway [28] and miR-21-5p dysregulation in exosomes augmented AKT kinase activity and impaired the regenerative activities [29]. We will further research the mechanism of microRNAs transported by exosomes derived from hUCMSCs in the repair of endometrial injury and practice the exosomes in vivo and in clinical therapy for endometrium injury.…”

Section: Stem Cells Internationalmentioning

confidence: 93%

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury

Wang

Xing

et al. 2020

Stem Cells International

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The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.

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Section: Stem Cells Internationalmentioning

confidence: 93%

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury

Wang

Xing

et al. 2020

Stem Cells International

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“…Apart from myo-miRs, various other miRs have been studied in this regard. MiR-21 with anti-apoptotic activity gets dysregulated in the exosomes derived from stromal cells in heart failure patients which significantly impair their regenerative capacity [108,109]. We have reported that MSCs modified for miR-210 overexpression, either by preconditioning or by genetic modification, transferred miR-210 to the adjacent cardiomyocytes in the co-culture as well as posttransplantation in the infarcted heart.…”

Section: Manipulation Of Mscs To Enhance Exosomal Mir Payloadmentioning

confidence: 99%

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

2020

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Bone marrow-derived mesenchymal stem cells (MSCs) have successfully progressed to phase III clinical trials successive to an intensive in vitro and pre-clinical assessment in experimental animal models of ischemic myocardial injury. With scanty evidence regarding their cardiogenic differentiation in the recipient patients' hearts post-engraftment, paracrine secretion of bioactive molecules is being accepted as the most probable underlying mechanism to interpret the beneficial effects of cell therapy. Secretion of small non-coding microRNA (miR) constitutes an integral part of the paracrine activity of stem cells, and there is emerging interest in miRs' delivery to the heart as part of cell-free therapy to exploit their integral role in various cellular processes. MSCs also release membrane vesicles of diverse sizes loaded with a wide array of miRs as part of their paracrine secretions primarily for intercellular communication and to shuttle genetic material. Exosomes can also be loaded with miRs of interest for delivery to the organs of interest including the heart, and hence, exosome-based cell-free therapy is being assessed for cell-free therapy as an alternative to cell-based therapy. This review of literature provides an update on cell-free therapy with primary focus on exosomes derived from BM-derived MSCs for myocardial repair.

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“…It is noteworthy to mention that in some cases, depending on cell-type as well as genotypic and functional status of the cells, specific components in the exosomes may not be beneficial but rather, harmful to the cardiovascular system (Barile et al, 2017a). For example, the progression of heart failure may alter the miRNA cargos in cardiac-derived exosomes and suppress their regenerative activities (Qiao et al, 2019). As an individual miRNA transferred via exosomes from different cell types or in different status may elicit divergent biological responses, exosomes extracted from the serum of dilated cardiomyopathy patients were reported not only to cause dramatic pathological changes in gene expression in both neonatal rat cardiomyocytes and hiPSC-CMs in vitro but were also associated with the accelerated heart failure progression in patients (Jiang et al, 2017).…”

Section: Anti-fibrotic Effects Of Ipsc-exosomesmentioning

confidence: 99%

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Fan

Zhang

Joshi

et al. 2020

Front. Cell Dev. Biol.

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The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.

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microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential

Cited by 211 publications

References 56 publications

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

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