Theranostics 2021; 11(13):6616-6631. doi:10.7150/thno.57701 This issue Cite

Research Paper

TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo

Ao Shi1,2,3*, Jialun Li4,9*, Xinyuan Qiu5, Michael Sabbah1,2, Soulmaz Boroumand1, Tony Chieh-Ting Huang4, Chunfeng Zhao6, Andre Terzic1,2,7,8, Atta Behfar1,2,7✉, Steven L Moran4✉

1. Van Cleve Cardiac Regenerative Medicine Program, Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA.
2. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
3. Department of Biochemistry and Molecular Biology, Mayo Graduate School of Biomedical Science, Mayo Clinic, Rochester, MN, USA.
4. Division of Plastic Surgery, Mayo Clinic, Rochester, MN, USA.
5. Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, China.
6. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
7. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
8. Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
9. Department of Plastic Surgery, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
*These authors contributed equally to this work.

Citation:
Shi A, Li J, Qiu X, Sabbah M, Boroumand S, Huang TCT, Zhao C, Terzic A, Behfar A, Moran SL. TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics 2021; 11(13):6616-6631. doi:10.7150/thno.57701. https://www.thno.org/v11p6616.htm
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Abstract

Graphic abstract

Rationale: With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor enriched exosome from finbrin gel was a promising strategy to promote wound healing.

Methods: To address this unsolved problem, we developed clinical-grade platelets exosome product (PEP), which was incorporate with injectable surgical fibrin sealant (TISSEEL), to promote chronic wound healing and complete skin regeneration. The PEP characterization stimulated cellular activities and in vivo rabbit ischemic wound healing capacity of TISSEEL-PEP were performed and analyzed.

Results: PEP, enriched with transforming growth factor beta (TGF-β), possessed exosomal characteristics including exosome size, morphology, and typical markers including CD63, CD9, and ALG-2-interacting protein X (Alix). In vitro, PEP significantly promoted cell proliferation, migration, tube formation, as well as skin organoid formation. Topical treatment of ischemic wounds with TISSEEL-PEP promoted full-thickness healing with the reacquisition of hair follicles and sebaceous glands. Superior to untreated and TISSEEL-only treated controls, TISSEEL-PEP drove cutaneous healing associated with collagen synthesis and restoration of dermal architecture. Furthermore, PEP promoted epithelial and vascular cell activity enhancing angiogenesis to restore blood flow and mature skin function. Transcriptome deconvolution of TISSEEL-PEP versus TISSEEL-only treated wounds prioritized regenerative pathways encompassing neovascularization, matrix remodeling and tissue growth.

Conclusion: This room-temperature stable, lyophilized exosome product is thus capable of delivering a bioactive transforming growth factor beta to drive regenerative events.

Keywords: exosome, wound healing, skin regeneration, translational medicine, cell-free therapy


Citation styles

APA
Shi, A., Li, J., Qiu, X., Sabbah, M., Boroumand, S., Huang, T.C.T., Zhao, C., Terzic, A., Behfar, A., Moran, S.L. (2021). TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics, 11(13), 6616-6631. https://doi.org/10.7150/thno.57701.

ACS
Shi, A.; Li, J.; Qiu, X.; Sabbah, M.; Boroumand, S.; Huang, T.C.T.; Zhao, C.; Terzic, A.; Behfar, A.; Moran, S.L. TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics 2021, 11 (13), 6616-6631. DOI: 10.7150/thno.57701.

NLM
Shi A, Li J, Qiu X, Sabbah M, Boroumand S, Huang TCT, Zhao C, Terzic A, Behfar A, Moran SL. TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics 2021; 11(13):6616-6631. doi:10.7150/thno.57701. https://www.thno.org/v11p6616.htm

CSE
Shi A, Li J, Qiu X, Sabbah M, Boroumand S, Huang TCT, Zhao C, Terzic A, Behfar A, Moran SL. 2021. TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics. 11(13):6616-6631.

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