Theranostics 2019; 9(23):6976-6990. doi:10.7150/thno.35305 This issue Cite

Research Paper

Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells

Yan Zhang1,2, Jia Xu1,2, Siying Liu1,2, Meikuang Lim5, Shuang Zhao2,3, Kaige Cui1,2, Kaiyue Zhang1,2, Lingling Wang3, Qian Ji4, Zhongchao Han5, Deling Kong2, Zongjin Li1,2✉, Na Liu1,2✉

1. School of Medicine, Nankai University, Tianjin, 300071, China
2. Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences Nankai University, Tianjin, 300071, China
3. College of Life Sciences, Nankai University, Tianjin, 300071, China
4. Department of Radiology, Tianjin First Central Hospital, Tianjin, China; 24 Fukang Road, Nankai District, Tianjin, 300071, China
5. Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing, 100176, China

Citation:
Zhang Y, Xu J, Liu S, Lim M, Zhao S, Cui K, Zhang K, Wang L, Ji Q, Han Z, Kong D, Li Z, Liu N. Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells. Theranostics 2019; 9(23):6976-6990. doi:10.7150/thno.35305. https://www.thno.org/v09p6976.htm
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Abstract

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Background: Embryonic stem cells (ES) have a great potential for cell-based therapies in a regenerative medicine. However, the ethical and safety issues limit its clinical application. ES-derived extracellular vesicles (ES-EVs) have been reported suppress cellular senescence. Mesenchymal stem cells (MSCs) are widely used for clinical cell therapy. In this study, we investigated the beneficial effects of ES-EVs on aging MSCs to further enhancing their therapeutic effects.

Methods: In vitro, we explored the rejuvenating effects of ES-EVs on senescent MSCs by senescence-associated β-gal (SA-β-gal) staining, immunostaining, and DNA damage foci analysis. The therapeutic effect of senescent MSC pre-treated with ES-EVs was also evaluated by using mouse cutaneous wound model.

Results: We found that ES-EVs significantly rejuvenated the senescent MSCs in vitro and improve the therapeutic effects of MSCs in a mouse cutaneous wound model. In addition, we also identified that the IGF1/PI3K/AKT pathway mediated the antisenescence effects of ES-EVs on MSCs.

Conclusions: Our results suggested that ES cells derived-extracellular vesicles possess the antisenescence properties, which significantly rejuvenate the senescent MSCs and enhance the therapeutic effects of MSCs. This strategy might emerge as a novel therapeutic strategy for MSCs clinical application.

Keywords: Cellular senescence, Mesenchymal stem cells, Embryonic stem cells, Extracellular vesicles, IGF1/PI3K/AKT pathway


Citation styles

APA
Zhang, Y., Xu, J., Liu, S., Lim, M., Zhao, S., Cui, K., Zhang, K., Wang, L., Ji, Q., Han, Z., Kong, D., Li, Z., Liu, N. (2019). Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells. Theranostics, 9(23), 6976-6990. https://doi.org/10.7150/thno.35305.

ACS
Zhang, Y.; Xu, J.; Liu, S.; Lim, M.; Zhao, S.; Cui, K.; Zhang, K.; Wang, L.; Ji, Q.; Han, Z.; Kong, D.; Li, Z.; Liu, N. Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells. Theranostics 2019, 9 (23), 6976-6990. DOI: 10.7150/thno.35305.

NLM
Zhang Y, Xu J, Liu S, Lim M, Zhao S, Cui K, Zhang K, Wang L, Ji Q, Han Z, Kong D, Li Z, Liu N. Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells. Theranostics 2019; 9(23):6976-6990. doi:10.7150/thno.35305. https://www.thno.org/v09p6976.htm

CSE
Zhang Y, Xu J, Liu S, Lim M, Zhao S, Cui K, Zhang K, Wang L, Ji Q, Han Z, Kong D, Li Z, Liu N. 2019. Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells. Theranostics. 9(23):6976-6990.

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