Dataset Information

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization.

ABSTRACT:

Background

Reconstruction of complex critical-size defects (CSD) in the craniofacial region is a major challenge, and soft tissue regeneration is crucial in determining the therapeutic outcomes of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) that are homologous to cells in craniofacial tissue and represent a promising source for craniofacial tissue regeneration. Exosomes, which contain compound bioactive compounds, are the key factors in stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue.

Methods

SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularization were detected by measuring the wound area and performing histological and immunofluorescence analysis on the palatal gingival CSD of mice. Real-time live-cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo-mediated EC angiogenesis in vitro were tested by immunofluorescence staining, Western blot, and pull-down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect vascularization and wound healing through cell division cycle 42 (Cdc42).

Results

We found that SCAP-Exo promoted tissue regeneration of palatal gingival CSD by enhancing vascularization in the early phase in vivo and that SCAP-Exo improved the angiogenic capacity of ECs in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via Cdc42 signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs and that the Cdc42 protein could be reused directly by recipient ECs, which resulted in the activation of Cdc42-dependent filopodium formation and elevation in cell migration of ECs.

Conclusion

This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used in a cell-free approach to optimize tissue regeneration in the clinic.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7821694 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization.

Liu Yao Y Zhuang Xueying X Yu Si S Yang Ning N Zeng Jianhong J Liu Xuemei X Chen Xu X

Stem cell research & therapy 20210122 1

<h4>Background</h4>Reconstruction of complex critical-size defects (CSD) in the craniofacial region is a major challenge, and soft tissue regeneration is crucial in determining the therapeutic outcomes of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) that are homologous to cells in craniofacial tissue and represent a promising source for craniofacial tissue regeneration. Exosomes, which contain compound bioactive compounds, are the ...[more]

PMID: 33482924

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Project description:The aim of this study was to investigate the effects of PLLA nanofibrous microspheres (NF-MS) as a cell delivery carrier in combination with controlled release of BMP-2 from PLGA microspheres on the induction of odontogenic differentiation of human stem cells of apical papilla (SCAP). Injectable NF-MS, which mimic the physical architecture of collagen fibers on the nano scale, were fabricated by combining thermally-induced phase separation techniques with an emulsification process. SCAP cultured in a monolayer or cultured on NF-MS in spinner flasks were treated with 100ng/ml BMP-2 in vitro. Odontogenic differentiation was characterized by measuring alkaline phosphatase activity, odontogenic gene expression levels, calcium content, and dentin sialophosphoprotein accumulation. The results demonstrated that BMP-2 enhanced human SCAP odontogenic differentiation both in monolayer culture and on 3D NF-MS in spinner flask culture in vitro. We also developed and tested a system combining NF-MS with controlled BMP-2 release for dentin regeneration in vivo. The results indicate that controlled release of BMP-2 promoted more mineralization and osteodentin formation compared to a BSA-releasing control in a dose-dependent and time-dependent manner. In summary, the NF-MS combined with controlled release of BMP-2 provides an excellent microenvironment for SCAP to regenerate dentin tissue.Tooth lesion and loss affect masticatory efficiency, speaking function, facial aesthetics and even psychological health. Current treatments depend on "inert" restorative materials, which do not have the healing capacity and may lead to the failure of the restorations over a long term. The aim of this study was to develop an injectable biomaterial and desired growth factor delivery system to support stem cells for mineralized dental tissue regeneration. The study showed that novel injectable and biodegradable nanofibrous microspheres and controlled release of BMP-2 synergistically induce the odontogenic differentiation of human stem cells from the apical papilla and mineralized tissue regeneration, demonstrating the potential of living dental tissue repair.

Dataset Information

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization.

Background

Methods

Results

Conclusion

Publications

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization.

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