Extracellular vesicles from mesenchymal stem cells activates VEGF receptors and accelerates recovery of hindlimb ischemia

Gangadaran, Prakash; Rajendran, Ramya Lakshmi; Lee, Ho Won; Kalimuthu, S; Hong, Chae Moon; Jeong, Shin Young; Lee, Sang‐Woo; Lee, Jaetae; Ahn, Byeong‐Cheol

doi:10.1016/j.jconrel.2017.08.022

Cited by 173 publications

(164 citation statements)

References 84 publications

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“…MSCs have shown great advantages for cell‐based strategies due to their easily acquisition, capacity for self‐renewal and multilineage differentiation (Frenette, Pinho, Lucas, & Scheiermann, ). Transplantation of MSCs has been reported to treat varieties of diseases, including hind‐limb ischemia (Gangadaran et al, ), myocardial infarction (Luo et al, ), traumatic brain injury (Shi et al, ), alcoholic cirrhosis (Suk et al, ), arthritis (Luz‐Crawford et al, ), and even cancer (Amara et al, ). However, MSCs have to undergo senescence processes due to increased replication (Stolzing, Coleman, & Scutt, ) or changes in the external microenvironment (Brandl, Meyer, Bechmann, Nerlich, & Angele, ), thus exhibited age‐related changes, such as increased apoptosis and senescence, decreased proliferation ability and paracrine signaling (Madonna et al, ; Stolzing, Jones, Mcgonagle, & Scutt, ).…”

Section: Discussionmentioning

confidence: 99%

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Yang

Wang

et al. 2020

J Tissue Eng Regen Med

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Bone marrow-derived mesenchymal stromal cells (MSCs) have been wildly applied to cell-based strategies for tissue engineering and regenerative medicine; however, they have to undergo the senescence process and thus appeared to be less therapeutic effective. HMGA2, a protein belonged to high mobility group A (HMGA) family, exhibits an inverse expression level related to embryonic development and acts as a developmental regulator in stem cell self-renewal progression. Therefore, we performed senescence-associated β-galactosidase (SA-β-gal) staining, transwell assay, to examine the changes of MSCs in different stages and then over-expressed HMGA2 in MSCs by lentivirus transfection. We found the percentage of SA-β-gal staining positive cells in MSCs from 24-month-old Sprague-Dawley (SD) rats (O-MSCs) was significantly higher compared with MSCs from 2-week-old SD rats (Y-MSCs), and the expression levels of P21 and P53, two senescence-related molecules, were also significantly up-regulated in O-MSCs than in Y-MSCs. In contrast, the HMGA2 expression level in O-MSCs was dramatically down-regulated in contrast to Y-MSCs. In additional, the migration ability in O-MSCs was significantly attenuated than in Y-MSCs. After successfully over-expressed HMGA2 in O-MSCs, the percentage of SAβ-gal staining positive cells and the expression levels of P21 and P53 were reduced, and the migration ability was improved compared with O-MSCs without treatment. Further, mRNA sequencing analysis revealed that overexpression of HMGA2 changed the expression of genes related to cell proliferation and senescence, such as Lyz2, Pf4, Rgs2, and Mstn. Knockdown of Rgs2 in HMGA2 overexpression O-MSCs could antagonize the protective effect of HMGA2 in the senescence process of O-MSCs.

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Section: Discussionmentioning

confidence: 99%

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Yang

Wang

et al. 2020

J Tissue Eng Regen Med

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“…According to the histological analysis of penis 1 month after IC injection, we found that the possible mechanism of MSC‐Exo alleviating oxidative stress damage might be through the mobilization of cavernous endogenous stem cells to differentiate into endothelial cells. MSCs have been shown to promote tissue angiogenesis by paracrine the vascular endothelial growth factor (VEGF) or exosome containing VEGF and specific miRNA . Vascular endothelial growth factor is a highly specific factor that has been shown to stimulate endothelial cells migrations and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell‐derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury

Liu

Zhao

Luo

et al. 2019

J Cellular Molecular Medi

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Erectile dysfunction (ED) is a common ageing male's disease, and vascular ED accounts for the largest proportion of all types of ED. One of the mechanisms of vascular ED in the clinic is arterial insufficiency, which mainly caused by atherosclerosis, trauma and surgical. Moreover, oxidative stress damage after tissue ischemia usually aggravated the progress of ED. As a new way of acellular therapy, mesenchymal stem cell‐derived exosomes (MSC‐Exos) have great potential in ED treatment. In the current study, we have explored the mechanism of MSC‐Exos therapy in a rat model of internal iliac artery injury‐induced ED. Compared with intracavernous (IC) injection of phosphate‐buffered saline after artery injury, of note, we observed that both mesenchymal stem cells (MSCs) and MSC‐Exos through IC injection could improve the erectile function to varying degrees. More specifically, IC injection MSC‐Exos could promote cavernous sinus endothelial formation, reduce the organization oxidative stress damage, and improve the nitric oxide synthase and smooth muscle content in the corpus cavernosum. With similar potency compared with the stem cell therapy and other unique advantages, IC injection of MSC‐ Exos could be an effective treatment to ameliorate erectile function in a rat model of arterial injury.

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“…Our data corroborate results published by Gangadaran. et al where MSCs-derived EVs increased cellular migration, proliferation, endothelial tube formation in vitro and enhanced angiogenesis in ischemic limb in vivo [28]. In addition, Lopatina T. et al reported that MSCs derived EVs could induce the formation of vessel-like structures in vitro and in vivo after the subcutaneous injection in mixture with Matrigel Matrix and human microvascular endothelial cells [29].…”

Section: Discussionmentioning

confidence: 99%

Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells

Gomzikova

Zhuravleva

Vorobev

et al. 2019

Preprint

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Background: The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyzed the morphology, size distribution, molecular composition and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix.

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Extracellular vesicles from mesenchymal stem cells activates VEGF receptors and accelerates recovery of hindlimb ischemia

Cited by 173 publications

References 84 publications

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Mesenchymal stem cell‐derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury

Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells

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