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Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs.

ABSTRACT: OBJECTIVES:Schwann cells (SCs) are the principal glial cells in peripheral nerve system, involved in neuropathies with great regenerative potential. Dental pulp cells have been reported to maintain neurogenic potential. In contrast, the regulatory role of SCs on human dental pulp cells (hDPCs) development remains undefined. MATERIALS AND METHODS:SC secretion and SC-derived extracellular vesicles (EVs) were collected and used to treat hDPCs; and proliferation and multiple differentiation of hDPCs were detected after EVs treatments. Finally, we analysed the proteomes of SC-EVs and SCs through mass spectrum. RESULTS:In this study, we found SC secretion showed a predominantly regulatory role on the development of hDPCs. Further, we identified EVs from SC secretion with similar function as SC secretion in regulating hDPCs proliferation and multipotency. And expression of transcription factor Oct4 was upregulated after treatment of both SC secretion and EVs, as well as Sox2 and Nanog. We detected abundant enrichment of Oct4 in EVs, which might be responsible for the upregulation of stem cell-related genes in hDPCs. Through proteome and western blot analysis, we found enriched TGF?s in EVs, indicating that accelerated hDPCs proliferation may be mediated by activated TGF?-Samd and TGF?-MAPK signalling. CONCLUSIONS:In summary, our study sheds light on critical regulatory ability of SC-derived EVs on hDPCs proliferation and multipotency, suggesting great implications for seeding cells used in tissue engineering.

SUBMITTER: Li Z

PROVIDER: S-EPMC6529079 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs.

Li Ziyue Z Liang Yan Y Pan Kuangwu K Li Hui H Yu Mei M Guo Weihua W Chen Guoqing G Tian Weidong W

Cell proliferation 20170801 4

<h4>Objectives</h4>Schwann cells (SCs) are the principal glial cells in peripheral nerve system, involved in neuropathies with great regenerative potential. Dental pulp cells have been reported to maintain neurogenic potential. In contrast, the regulatory role of SCs on human dental pulp cells (hDPCs) development remains undefined.<h4>Materials and methods</h4>SC secretion and SC-derived extracellular vesicles (EVs) were collected and used to treat hDPCs; and proliferation and multiple different ...[more]

PMID: 28714175

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Project description:Cardiac mesenchymal stem cells (C-MSCs) are a novel mesenchymal stem cell (MSC) subpopulation derived from cardiac tissue, which are reported to be responsible for cardiac regeneration. Notch signaling is believed to aid in cardiac repair following myocardial injury. In this study, we have investigated the role of extracellular vesicles (EVs) from Notch1 engineered C-MSCs on angiogenesis and cardiomyocyte (CM) proliferation in ischemic myocardium. C-MSCs were isolated from Notch1flox mice (C-MSCNotch1 FF). Notch1 gene deletion was accomplished by adenoviral vector-mediated Cre recombination, and Notch1 overexpression was achieved by overexpression of Notch1 intracellular domain (N1ICD). EVs were isolated by using the size exclusion column method. Proteomic composition of EV was carried out by mass spectrometry. A mouse myocardial infarction (MI) model was generated by permanent left anterior descending (LAD) coronary artery ligation. Intramyocardial transplantation of Notch1 knockout C-MSCs (C-MSCsNotch1 KO) did not have any effect on cardiac function and scar size. On the other hand, transplantation of N1ICD-overexpressing C-MSCs (C-MSCsN1ICD) showed significant improvement in cardiac function and attenuation of fibrosis as compared to the control (PBS) group and non-modified C-MSC groups. C-MSCsN1ICD differentiated into smooth muscle cells and formed new vessels. Proteomics profiling identified several proteins, such as lysyl oxidase homolog-2 and biglycan, as highly enriched proteins in EV-C-MSCsN1ICD. Go term analysis indicated that EV-C-MSCsN1ICD were enriched with bioactive factors, potent pro-repair proteins responsible for cell migration and proliferation. EV-C-MSCs Notch1FF and EV-C-MSCsN1ICD were strongly proangiogenic under both in vitro and in vivo conditions. EV-C-MSCsN1ICD caused dense tube formation in vitro and increased neovasculogenesis in the peri-infarct area in vivo. Furthermore, EV-C-MSCsN1ICD attenuated endothelial cell (EC) and CM apoptosis under oxidative stress and ischemic injury. Similarly, EV-C-MSCNotch1 FF and EV-C-MSCN1ICD treatment improved cardiac function and decreased fibrosis in mice post-MI. EV-C-MSCsN1ICD were very effective in improving cardiac function and decreasing fibrosis. Notch1 signaling is a strong stimulus for cardiac regeneration by C-MSCs. EVs secreted by Notch1-overexpressing C-MSCs were highly effective in preventing cell death, promoting angiogenesis and CM proliferation, and restoring cardiac function post-MI. Overall, these results suggest that Notch1 overexpression may further enhance the effectiveness of EVs secreted by C-MSCs in cell-free therapy.

Dataset Information

Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs.

Publications

Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs.

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