Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function

Qu, Qingxi; Pang, Yingxin; Zhang, Chunmei; Liu, Linghong; Bi, Yanwen

doi:10.1186/s13287-020-01639-1

Cited by 46 publications

(50 citation statements)

References 44 publications

(62 reference statements)

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“…Many studies have proved that exosomes secreted by MSCs may be a key ingredient of paracrine mechanism to spread its repair function, exosomes can be served as a translocator(miRNAs, lncRNAs, and proteins) that contributes to intercellular communication 26,27 . Our previous studies have found that exosome cargo may account for the vascular protective effect of hucMSCs against vein graft failure 14 .…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Isolation, characterization and culture of hucMSCs and HUVECs All experiment protocols were approved by the Ethical Committee of the Qilu Hospital of Shandong University (KYLL-2017-106) as we have described 14 . Human umbilical cords were collected from informed, consenting delivery woman and processed as we have previously described 14 . Human umbilical cord mesenchymal stem cells (hucMSCs) and human umbilical vein endothelial cells (HUVECs )were isolated, cultured ,thawed and expanded following the established method 15 .The hucMSCs were cultured in alpha-minimum essential medium (α-MEM) containing 10% fetal bovine serum (FBS) in a humidi ed atmosphere at 37°C and 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

“…hucMSCs-exosomes were extracted from supernatants of cell cultures by ultracentrifugation method as we have described 17 . The morphology hucMSCs-exosomes were observed under a transmission electron microscope (Hitachi,Japan) by an experienced engineer.…”

Section: Extraction and Identi Cation Of Hucmsc-exosomesmentioning

confidence: 99%

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miRNA-126-3p Carried by Human Umbilical Cord Mesenchymal Stem Cell Enhances Endothelial Function through Exosome-mediated Mechanisms in Vitro and Attenuates Vein Grafts Neointimal Formation in Vivo

Wang

Bing

et al. 2020

Preprint

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Background: The aim of this study was to determine whether the combination of MSC implantation with miRNA-126-3p overexpression would further improve the surgical results after vein grafting. Methods: hucMSCs and HUVECs were isolated from human umbilical cords and characterized by a series of experiments. Lentivirus vector encoding miRNA-126-3p was transfected into hucMSCs and verified by PCR. We analyzed the miRNA-126-3p-hucMSC function in vascular endothelial cells by using a series of co-culture experiments. miRNA-126-3p-hucMSCs-exosomes were separated from cell culture supernatants and identified by WB and TEM. We validated the role of miRNA-126-3p-hucMSCs-exosomes on HUVECs proliferative and migratory and angiogenic activities by using a series of function experiments. We further performed co-culture experiments to detect downstream target genes and signaling pathways of miRNA-126-3p-hucMSCs in HUVECs. We established a rat vein grafting model, CM-Dil-labeled hucMSCs were injected intravenously into rats and the transplanted cells homing to the vein grafts were detected by fluorescent microscopy. We performed historical and immunohistochemical experiments to exam miRNA-126-3p-hucMSC transplantation on vein grafts neointimal formation and reendothelialization in vitro. Results: We successfully isolated and identified primary hucMSCs and HUVECs. Primary hucMSCs were transfected with lentiviral vectors carrying miRNA-126-3p at a MOI 75. Co-culture studies indicated that overexpression of miRNA-126-3p in hucMSCs enhanced HUVECs proliferation, migration and tube formation in vivo. We successfully separated hucMSCs-exosomes and found that miRNA-126-3p-hucMSCs-exosomes can strengthen the proliferative, migratory, and tube formation capacities of HUVECs. Further PCR and WB analysis indicated that, SPRED-1/PIK3R2/AKT/ ERK1/2 pathways are involved in this process. In the rat vein arterialization model, reendothelialization analysis showed that transplantation with hucMSCs modified with miRNA-126-3p had a higher reendothelialization of the vein grafts. The subsequent historical and immunohistochemical examination revealed that delivery with miRNA-126-3p overexpressed hucMSCs significantly reduced vein graft intimal hyperplasia in rats. Conclusion: These results suggest hucMSC-based miRNA-126-3p gene therapy may be a novel option for the treatment of vein graft disease after CABG.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Extraction and Identi Cation Of Hucmsc-exosomesmentioning

confidence: 99%

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miRNA-126-3p Carried by Human Umbilical Cord Mesenchymal Stem Cell Enhances Endothelial Function through Exosome-mediated Mechanisms in Vitro and Attenuates Vein Grafts Neointimal Formation in Vivo

Wang

Bing

et al. 2020

Preprint

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“…Thus, we assumed that BMSCs might be able to differentiate into enterocytes to repair intestinal epithelial barrier. According to previous reports, PI3K/AKT/mTOR signaling pathway is involved in cell fate and likely to be associated with proliferation and differentiation of stem cells [21,22]. To investigate whether the PI3K/AKT/mTOR signaling pathway is associated with the differentiation of BMSCs into enterocytes, we performed the transwell co-culture system and evaluated the characteristic molecules of enterocytes by immuno uorescence staining.…”

Section: Association Of Pi3k/akt/mtor Signal Pathway In the Differentmentioning

confidence: 99%

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

Jiang¹,

Xia²,

Yang³

et al. 2020

Preprint

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Background Endotoxemia based on liver failure has been reported to be related to the worse clinical outcomes, but its management remains unsatisfactory. The addition of bone marrow mesenchymal stem cells (BMSCs) could promote the recovery of liver function and increase the survival with the liver failure. However, little is known about the potential of cell therapy with endotoxemia based on liver failure. Methods BMSCs were isolated from rats, and their morphology, differentiation potential, surface markers, and cell cycle were assayed. Thioacetamide-induced acute liver failure rats were randomized to groups with or without BMSCs. During the experiment, survival was recorded. Diamine oxidase (DAO), endotoxin, interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) and tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), histology, and western blot. Bromodeoxynucleoside uracil (BrdU) incorporation assay was performed to observe the migration of BMSCs. The intestinal epithelial differentiation of BMSCs was induced by co culture with small intestinal crypt in rats (IEC-6). Immunofluorescence was used to analyze the expression of intestinal endothelial markers. Western blot analysis was further performed to examine the differentiation effect when inhibiting the phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Results BrdU-traced BMSCs targeted migrate to intestinal injury sites. Mortality was significantly decreased and intestinal damage was repaired following BMSCs transplantation. Proteomics revealed higher expression of DAO, endotoxin, IL-6 and TNF-α in the model animals, but these changes were reversed after BMSCs transplantation. In the in vitro study, the intestinal epithelial differentiation of BMSCs was exhibited following co-culture. Moreover, the blocking of PI3K/AKT/mTOR signal pathway inhibited this differentiation. Conclusions These evidences indicate that BMSCs eliminate endotoxemia and reduce mortality in the animal model of acute liver failure by reducing intestine damage.

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Application of exosomes for the alleviation of COVID‐19‐related pathologies

Rezabakhsh

Mahdipour

Nourazarian

et al. 2022

Cell Biochemistry & Function

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The pandemic of COVID‐19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti‐inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID‐19 pathologies.

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Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function

Cited by 46 publications

References 44 publications

miRNA-126-3p Carried by Human Umbilical Cord Mesenchymal Stem Cell Enhances Endothelial Function through Exosome-mediated Mechanisms in Vitro and Attenuates Vein Grafts Neointimal Formation in Vivo

miRNA-126-3p Carried by Human Umbilical Cord Mesenchymal Stem Cell Enhances Endothelial Function through Exosome-mediated Mechanisms in Vitro and Attenuates Vein Grafts Neointimal Formation in Vivo

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

Application of exosomes for the alleviation of COVID‐19‐related pathologies

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