The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway
Open accessAbstract
Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted β-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and β-catenin and the decreased expression of E-cadherin. The activation of Wnt/β-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by β-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated β-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. Significance: Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, it is reported that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be one of the important mechanisms responsible for cutaneous wound healing.
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Cites
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Exosomes – vesicular carriers for intercellular communication
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Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2009.12.003 · Cited by 2,215
Endothelial Cell Migration During Angiogenesis
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Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration
Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., Buchanan, M., Hosein, A. N., Basik, M., & Wrana, J. L. (2012) · Cell · doi:10.1016/j.cell.2012.11.024 · Cited by 1,311
Active Wnt proteins are secreted on exosomes
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Exosomes: endosomal-derived vesicles shipping extracellular messages
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Cited by
Concise review: MSC-derived exosomes for cell-free therapy
Phinney, D. G., & Pittenger, M. F. (2017) · Stem Cells · doi:10.1002/stem.2575 · Cited by 1,834
Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper
Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F. A., del Portillo, H. A., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.30087 · Cited by 1,491
Yang, J., Chen, Z., Pan, D., Li, H., & Shen, J. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s249129 · Cited by 522
The Role of MSC in Wound Healing, Scarring and Regeneration
Guillamat-Prats, R. (2021) · Cells · doi:10.3390/cells10071729 · Cited by 393
Tsiapalis, D., & O’Driscoll, L. (2020) · Cells · doi:10.3390/cells9040991 · Cited by 313
Metadata
- Authors
- Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., Zhu, Y., Wu, L., Pan, Z., Zhu, W., Qian, H., & Xu, W.
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-03-30
- Volume
- 4
- Issue
- 5
- Pages
- 513-522
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- OpenAlex
- W2131069942
- Cited by
- 477
- References
- 50
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., Zhu, Y., Wu, L., Pan, Z., Zhu, W., Qian, H., & Xu, W. (2015). Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway. Stem Cells Translational Medicine. https://doi.org/10.5966/sctm.2014-0267
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