Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons
Abstract
:1. Introduction
2. Results
2.1. Characterization of ADSC-EVs
2.2. ADSC-EVs Promote the Proliferation of Tenocyte
2.3. ADSC-EVs Improve Tenocyte Migration Ability
2.4. ADSC-EVs Improve the Mechanical Strength of Repaired Tendon In Vivo
2.5. ADSC-EVs Increase the Expression of Tenomodulin, Biglycan and Decorin In Vivo
3. Discussion
4. Materials and Methods
4.1. Animal Experiments/Ethics
4.2. Harvest of ADSCs
4.3. Preparation of ADSC Derived EVs
4.4. Characterization of ADSC-Derived EVs
4.5. Tenocyte Proliferation Assay
4.6. Tenocyte Migration Assay
4.7. Animal Study
4.8. Protein Expression Analysis of EV-Treated Tendon
4.8.1. Total Collagen Assay
4.8.2. Western Blot
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Screen, H.R.C.; Berk, D.E.; Kadler, K.E.; Ramirez, F.; Young, M.F. Tendon Functional Extracellular Matrix. J. Orthop. Res. 2015, 33, 793–799. [Google Scholar] [CrossRef] [Green Version]
- Kastelic, J.; Galeski, A.; Baer, E. The multicomposite structure of tendon. Connect. Tissue Res. 1978, 6, 11–23. [Google Scholar] [CrossRef]
- Sharma, P.; Maffulli, N. Tendon injury and tendinopathy: Healing and repair. J. Bone Jt. Surg. Am. 2005, 87, 187–202. [Google Scholar] [CrossRef] [Green Version]
- Manning, C.N.; Martel, C.; Sakiyama-Elbert, S.E.; Silva, M.J.; Shah, S.; Gelberman, R.H.; Thomopoulos, S. Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro. Stem Cell Res. Ther. 2015, 6, 74. [Google Scholar] [CrossRef] [Green Version]
- Lim, W.L.; Liau, L.L.; Ng, M.H.; Chowdhury, S.R.; Law, J.X. Current Progress in Tendon and Ligament Tissue Engineering. Tissue Eng. Regen. Med. 2019, 16, 549–571. [Google Scholar] [CrossRef]
- Chamberlain, G.; Fox, J.; Ashton, B.; Middleton, J. Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007, 25, 2739–2749. [Google Scholar] [CrossRef] [Green Version]
- Huang, Y.; He, B.; Wang, L.; Yuan, B.; Shu, H.; Zhang, F.; Sun, L. Bone marrow mesenchymal stem cell-derived exosomes promote rotator cuff tendon-bone healing by promoting angiogenesis and regulating M1 macrophages in rats. Stem Cell Res. Ther. 2020, 11, 496. [Google Scholar] [CrossRef] [PubMed]
- Maruyama, M.; Wei, L.; Thio, T.; Storaci, H.W.; Ueda, Y.; Yao, J. The Effect of Mesenchymal Stem Cell Sheets on Early Healing of the Achilles Tendon in Rats. Tissue Eng. Part A 2020, 26, 206–213. [Google Scholar] [CrossRef] [PubMed]
- Chamberlain, C.S.; Saether, E.E.; Aktas, E.; Vanderby, R. Mesenchymal Stem Cell Therapy on Tendon/Ligament Healing. J. Cytokine Biol. 2017, 2. [Google Scholar] [CrossRef]
- Tang, Y.; Chen, C.; Liu, F.; Xie, S.; Qu, J.; Li, M.; Li, Z.; Li, X.; Shi, Q.; Li, S.; et al. Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing. Biomaterials 2020, 241, 119837. [Google Scholar] [CrossRef]
- Chen, G.; Zhang, W.; Zhang, K.; Wang, S.; Gao, Y.; Gu, J.; He, L.; Li, W.; Zhang, C.; Zhang, W.; et al. Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits. Stem Cells Int. 2020, 2020, 8822609. [Google Scholar] [CrossRef]
- Maxson, S.; Lopez, E.A.; Yoo, D.; Danilkovitch-Miagkova, A.; Leroux, M.A. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Transl. Med. 2012, 1, 142–149. [Google Scholar] [CrossRef] [PubMed]
- Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies. Tissue Eng. 2001, 7, 211–228. [CrossRef] [Green Version]
- Uysal, C.A.; Tobita, M.; Hyakusoku, H.; Mizuno, H. Adipose-derived stem cells enhance primary tendon repair: Biomechanical and immunohistochemical evaluation. J. Plast. Reconstr. Aesthet. Surg. 2012, 65, 1712–1719. [Google Scholar] [CrossRef] [PubMed]
- De Mattos Carvalho, A.; Alves, A.L.G.; de Oliveira, P.G.G.; Cisneros Álvarez, L.E.; Amorim, R.L.; Hussni, C.A.; Deffune, E. Use of Adipose Tissue-Derived Mesenchymal Stem Cells for Experimental Tendinitis Therapy in Equines. J. Equine Vet. Sci. 2011, 31, 26–34. [Google Scholar] [CrossRef] [Green Version]
- Uysal, A.C.; Mizuno, H. Tendon regeneration and repair with adipose derived stem cells. Curr. Stem Cell Res. Ther. 2010, 5, 161–167. [Google Scholar] [CrossRef] [PubMed]
- Timmers, L.; Lim, S.K.; Arslan, F.; Armstrong, J.S.; Hoefer, I.E.; Doevendans, P.A.; Piek, J.J.; El Oakley, R.M.; Choo, A.; Lee, C.N.; et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 2007, 1, 129–137. [Google Scholar] [CrossRef] [Green Version]
- Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; et al. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells 2015, 33, 2158–2168. [Google Scholar] [CrossRef]
- Ha, D.H.; Kim, H.K.; Lee, J.; Kwon, H.H.; Park, G.H.; Yang, S.H.; Jung, J.Y.; Choi, H.; Lee, J.H.; Sung, S.; et al. Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells 2020, 9, 1157. [Google Scholar] [CrossRef]
- Caplan, A.I.; Correa, D. The MSC: An injury drugstore. Cell Stem Cell 2011, 9, 11–15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phinney, D.G.; Pittenger, M.F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells 2017, 35, 851–858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Caplan, A.I.; Dennis, J.E. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 2006, 98, 1076–1084. [Google Scholar] [CrossRef]
- Gnecchi, M.; He, H.; Liang, O.D.; Melo, L.G.; Morello, F.; Mu, H.; Noiseux, N.; Zhang, L.; Pratt, R.E.; Ingwall, J.S.; et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med. 2005, 11, 367–368. [Google Scholar] [CrossRef] [PubMed]
- Ionescu, L.; Byrne, R.N.; van Haaften, T.; Vadivel, A.; Alphonse, R.S.; Rey-Parra, G.J.; Weissmann, G.; Hall, A.; Eaton, F.; Thébaud, B. Stem cell conditioned medium improves acute lung injury in mice: In vivo evidence for stem cell paracrine action. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012, 303, L967–l977. [Google Scholar] [CrossRef] [Green Version]
- Chang, C.P.; Chio, C.C.; Cheong, C.U.; Chao, C.M.; Cheng, B.C.; Lin, M.T. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin. Sci. 2013, 124, 165–176. [Google Scholar] [CrossRef]
- Yanez-Mo, M.; Siljander, P.R.; Andreu, Z.; Zavec, A.B.; Borras, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [Green Version]
- Raposo, G.; Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013, 200, 373–383. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keshtkar, S.; Azarpira, N.; Ghahremani, M.H. Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine. Stem Cell Res. Ther. 2018, 9, 63. [Google Scholar] [CrossRef]
- Bruno, S.; Kholia, S.; Deregibus, M.C.; Camussi, G. The Role of Extracellular Vesicles as Paracrine Effectors in Stem Cell-Based Therapies. Adv. Exp. Med. Biol. 2019, 1201, 175–193. [Google Scholar] [CrossRef]
- Yin, L.; Liu, X.; Shi, Y.; Ocansey, D.K.W.; Hu, Y.; Li, X.; Zhang, C.; Xu, W.; Qian, H. Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine. Cells 2020, 9, 707. [Google Scholar] [CrossRef] [Green Version]
- Chen, B.; Cai, J.; Wei, Y.; Jiang, Z.; Desjardins, H.E.; Adams, A.E.; Li, S.; Kao, H.K.; Guo, L. Exosomes Are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-Regulating Early Inflammation and Angiogenesis. Plast. Reconstr. Surg. 2019, 144, 816e–827e. [Google Scholar] [CrossRef]
- Vizoso, F.J.; Eiro, N.; Cid, S.; Schneider, J.; Perez-Fernandez, R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int. J. Mol. Sci. 2017, 18, 1852. [Google Scholar] [CrossRef] [Green Version]
- Xu, R.; Greening, D.W.; Zhu, H.J.; Takahashi, N.; Simpson, R.J. Extracellular vesicle isolation and characterization: Toward clinical application. J. Clin. Investig. 2016, 126, 1152–1162. [Google Scholar] [CrossRef] [Green Version]
- Thery, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Kowal, J.; Arras, G.; Colombo, M.; Jouve, M.; Morath, J.P.; Primdal-Bengtson, B.; Dingli, F.; Loew, D.; Tkach, M.; Thery, C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc. Natl. Acad. Sci. USA 2016, 113, E968–E977. [Google Scholar] [CrossRef] [Green Version]
- Riley, G.P.; Harrall, R.L.; Constant, C.R.; Chard, M.D.; Cawston, T.E.; Hazleman, B.L. Tendon degeneration and chronic shoulder pain: Changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann. Rheum. Dis. 1994, 53, 359–366. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.H.C. Mechanobiology of tendon. J. Biomech. 2006, 39, 1563–1582. [Google Scholar] [CrossRef] [PubMed]
- Lin, D.; Alberton, P.; Caceres, M.D.; Volkmer, E.; Schieker, M.; Docheva, D. Tenomodulin is essential for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing. Cell Death Dis. 2017, 8, e3116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Docheva, D.; Hunziker, E.B.; Fassler, R.; Brandau, O. Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol. Cell Biol. 2005, 25, 699–705. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pechanec, M.Y.; Boyd, T.N.; Baar, K.; Mienaltowski, M.J. Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro. BMC Musculoskelet. Disord. 2020, 21, 627. [Google Scholar] [CrossRef] [PubMed]
- Salimi, H.; Suzuki, A.; Habibi, H.; Orita, K.; Hori, Y.; Yabu, A.; Terai, H.; Tamai, K.; Nakamura, H. Biglycan expression and its function in human ligamentum flavum. Sci. Rep. 2021, 11, 4867. [Google Scholar] [CrossRef] [PubMed]
- Andarawis-Puri, N.; Flatow, E.L.; Soslowsky, L.J. Tendon basic science: Development, repair, regeneration, and healing. J. Orthop. Res. 2015, 33, 780–784. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, S.H.; Chou, P.Y.; Chen, Z.Y.; Lin, F.H. Electrospun Water-Borne Polyurethane Nanofibrous Membrane as a Barrier for Preventing Postoperative Peritendinous Adhesion. Int. J. Mol. Sci. 2019, 20, 1625. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chou, P.Y.; Chen, S.H.; Chen, C.H.; Chen, S.H.; Fong, Y.T.; Chen, J.P. Thermo-responsive in-situ forming hydrogels as barriers to prevent post-operative peritendinous adhesion. Acta Biomater. 2017, 63, 85–95. [Google Scholar] [CrossRef]
- Chamberlain, C.S.; Clements, A.E.B.; Kink, J.A.; Choi, U.; Baer, G.S.; Halanski, M.A.; Hematti, P.; Vanderby, R. Extracellular Vesicle-Educated Macrophages Promote Early Achilles Tendon Healing. Stem Cells 2019, 37, 652–662. [Google Scholar] [CrossRef] [Green Version]
- Shi, Z.; Wang, Q.; Jiang, D. Extracellular vesicles from bone marrow-derived multipotent mesenchymal stromal cells regulate inflammation and enhance tendon healing. J. Transl. Med. 2019, 17, 211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, H.; Yoneda, S.; Abu-Amer, Y.; Guilak, F.; Gelberman, R.H. Stem cell-derived extracellular vesicles attenuate the early inflammatory response after tendon injury and repair. J. Orthop. Res. 2020, 38, 117–127. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Hu, Q.; Song, W.; Yu, W.; He, Y. Adipose Stem Cell-Derived Exosomes Decrease Fatty Infiltration and Enhance Rotator Cuff Healing in a Rabbit Model of Chronic Tears. Am. J. Sports Med. 2020, 48, 1456–1464. [Google Scholar] [CrossRef]
- Chamberlain, C.S.; Kink, J.A.; Wildenauer, L.A.; McCaughey, M.; Henry, K.; Spiker, A.M.; Halanski, M.A.; Hematti, P.; Vanderby, R. Exosome-educated macrophages and exosomes differentially improve ligament healing. Stem Cells 2021, 39, 55–61. [Google Scholar] [CrossRef] [PubMed]
- Yu, H.; Cheng, J.; Shi, W.; Ren, B.; Zhao, F.; Shi, Y.; Yang, P.; Duan, X.; Zhang, J.; Fu, X.; et al. Bone marrow mesenchymal stem cell-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells. Acta Biomat. 2020, 106, 328–341. [Google Scholar] [CrossRef]
- Zhang, M.; Liu, H.; Cui, Q.; Han, P.; Yang, S.; Shi, M.; Zhang, T.; Zhang, Z.; Li, Z. Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon. Stem Cell Res. Ther. 2020, 11, 402. [Google Scholar] [CrossRef]
- Chang, C.H.; Tsai, W.C.; Lin, M.S.; Hsu, Y.H.; Pang, J.H. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J. Appl. Physiol. 2011, 110, 774–780. [Google Scholar] [CrossRef] [Green Version]
- Wu, Y.F.; Chen, C.H.; Cao, Y.; Avanessian, B.; Wang, X.T.; Tang, J.B. Molecular events of cellular apoptosis and proliferation in the early tendon healing period. J. Hand Surg. Am. 2010, 35, 2–10. [Google Scholar] [CrossRef]
- Nourissat, G.; Berenbaum, F.; Duprez, D. Tendon injury: From biology to tendon repair. Nat. Rev. Rheumatol. 2015, 11, 223–233. [Google Scholar] [CrossRef] [PubMed]
- Durgam, S.; Stewart, M. Cellular and Molecular Factors Influencing Tendon Repair. Tissue Eng. Part B Rev. 2017, 23, 307–317. [Google Scholar] [CrossRef]
- Xu, P.; Deng, B.; Zhang, B.; Luo, Q.; Song, G. Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling. Int. J. Mol. Sci. 2021, 22, 4928. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.Y.; Chen, S.H.; Chen, C.H.; Chou, P.Y.; Yang, C.C.; Lin, F.H. Polysaccharide Extracted from Bletilla striata Promotes Proliferation and Migration of Human Tenocytes. Polymers 2020, 12, 2567. [Google Scholar] [CrossRef]
- Chen, Q.; Liang, Q.; Zhuang, W.; Zhou, J.; Zhang, B.; Xu, P.; Ju, Y.; Morita, Y.; Luo, Q.; Song, G. Tenocyte proliferation and migration promoted by rat bone marrow mesenchymal stem cell-derived conditioned medium. Biotechnol. Lett. 2018, 40, 215–224. [Google Scholar] [CrossRef] [PubMed]
- Ren, S.; Chen, J.; Duscher, D.; Liu, Y.; Guo, G.; Kang, Y.; Xiong, H.; Zhan, P.; Wang, Y.; Wang, C.; et al. Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways. Stem Cell Res. Ther. 2019, 10, 47. [Google Scholar] [CrossRef]
- Chen, S.H.; Chou, P.Y.; Chen, Z.Y.; Chuang, D.C.; Hsieh, S.T.; Lin, F.H. An electrospun nerve wrap comprising Bletilla striata polysaccharide with dual function for nerve regeneration and scar prevention. Carbohydr. Polym. 2020, 250, 116981. [Google Scholar] [CrossRef] [PubMed]
- Shalumon, K.T.; Sheu, C.; Chen, C.H.; Chen, S.H.; Jose, G.; Kuo, C.Y.; Chen, J.P. Multi-functional electrospun antibacterial core-shell nanofibrous membranes for prolonged prevention of post-surgical tendon adhesion and inflammation. Acta Biomater. 2018, 72, 121–136. [Google Scholar] [CrossRef] [PubMed]
- Ren, Y.; Zhang, S.; Wang, Y.; Jacobson, D.S.; Reisdorf, R.L.; Kuroiwa, T.; Behfar, A.; Moran, S.L.; Steinmann, S.P.; Zhao, C. Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo. Biomaterials 2021, 276, 121019. [Google Scholar] [CrossRef] [PubMed]
- Kew, S.J.; Gwynne, J.H.; Enea, D.; Brookes, R.; Rushton, N.; Best, S.M.; Cameron, R.E. Synthetic collagen fascicles for the regeneration of tendon tissue. Acta Biomater. 2012, 8, 3723–3731. [Google Scholar] [CrossRef]
- Maffulli, N.; Ewen, S.W.; Waterston, S.W.; Reaper, J.; Barrass, V. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing. Am. J. Sports Med. 2000, 28, 499–505. [Google Scholar] [CrossRef] [PubMed]
- Yin, H.; Caceres, M.D.; Yan, Z.; Schieker, M.; Nerlich, M.; Docheva, D. Tenomodulin regulates matrix remodeling of mouse tendon stem/progenitor cells in an ex vivo collagen I gel model. Biochem. Biophys. Res. Commun. 2019, 512, 691–697. [Google Scholar] [CrossRef]
- Dex, S.; Alberton, P.; Willkomm, L.; Sollradl, T.; Bago, S.; Milz, S.; Shakibaei, M.; Ignatius, A.; Bloch, W.; Clausen-Schaumann, H.; et al. Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load. EBioMedicine 2017, 20, 240–254. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hou, Y.; Ni, M.; Lin, S.; Sun, Y.; Lin, W.; Liu, Y.; Wang, H.; He, W.; Li, G.; Xu, L. Tenomodulin highly expressing MSCs as a better cell source for tendon injury healing. Oncotarget 2017, 8, 77424–77435. [Google Scholar] [CrossRef] [Green Version]
- Alexandrov, V.P.; Naimov, S.I. A Prospectus of Tenomodulin. Folia Med. 2016, 58, 19–27. [Google Scholar] [CrossRef] [Green Version]
- Dunkman, A.A.; Buckley, M.R.; Mienaltowski, M.J.; Adams, S.M.; Thomas, S.J.; Satchell, L.; Kumar, A.; Pathmanathan, L.; Beason, D.P.; Iozzo, R.V.; et al. The tendon injury response is influenced by decorin and biglycan. Ann. Biomed. Eng. 2014, 42, 619–630. [Google Scholar] [CrossRef] [Green Version]
- Hong, P.; Yang, H.; Wu, Y.; Li, K.; Tang, Z. The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: A comprehensive review. Stem Cell Res. Ther. 2019, 10, 242. [Google Scholar] [CrossRef] [PubMed]
- Shukla, L.; Yuan, Y.; Shayan, R.; Greening, D.W.; Karnezis, T. Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration. Front Pharmacol. 2020, 11, 158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xiong, M.; Zhang, Q.; Hu, W.; Zhao, C.; Lv, W.; Yi, Y.; Wu, Y.; Wu, M. Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery. Front Cell Dev. Biol. 2020, 8, 574223. [Google Scholar] [CrossRef]
- Mazini, L.; Rochette, L.; Amine, M.; Malka, G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int. J. Mol. Sci. 2019, 20, 2523. [Google Scholar] [CrossRef] [Green Version]
- Jafarinia, M.; Alsahebfosoul, F.; Salehi, H.; Eskandari, N.; Ganjalikhani-Hakemi, M. Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy. Immunol. Investig. 2020, 49, 758–780. [Google Scholar] [CrossRef] [PubMed]
- Gissi, C.; Radeghieri, A.; Antonetti Lamorgese Passeri, C.; Gallorini, M.; Calciano, L.; Oliva, F.; Veronesi, F.; Zendrini, A.; Cataldi, A.; Bergese, P.; et al. Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study. PLoS ONE 2020, 15, e0229914. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.; Kang, X.; Wang, Y.; Bian, X.; He, G.; Zhou, M.; Tang, K. Exosomes Derived from Bone Marrow Stromal Cells (BMSCs) Enhance Tendon-Bone Healing by Regulating Macrophage Polarization. Med. Sci. Monit. 2020, 26, e923328. [Google Scholar] [CrossRef] [PubMed]
- Del Fattore, A.; Luciano, R.; Saracino, R.; Battafarano, G.; Rizzo, C.; Pascucci, L.; Alessandri, G.; Pessina, A.; Perrotta, A.; Fierabracci, A.; et al. Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells. Expert. Opin. Biol. Ther. 2015, 15, 495–504. [Google Scholar] [CrossRef]
- Pomatto, M.; Gai, C.; Negro, F.; Cedrino, M.; Grange, C.; Ceccotti, E.; Togliatto, G.; Collino, F.; Tapparo, M.; Figliolini, F.; et al. Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes. Int. J. Mol. Sci. 2021, 22, 3851. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chen, S.-H.; Chen, Z.-Y.; Lin, Y.-H.; Chen, S.-H.; Chou, P.-Y.; Kao, H.-K.; Lin, F.-H. Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons. Int. J. Mol. Sci. 2021, 22, 12373. https://doi.org/10.3390/ijms222212373
Chen S-H, Chen Z-Y, Lin Y-H, Chen S-H, Chou P-Y, Kao H-K, Lin F-H. Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons. International Journal of Molecular Sciences. 2021; 22(22):12373. https://doi.org/10.3390/ijms222212373
Chicago/Turabian StyleChen, Shih-Heng, Zhi-Yu Chen, Ya-Hsuan Lin, Shih-Hsien Chen, Pang-Yun Chou, Huang-Kai Kao, and Feng-Huei Lin. 2021. "Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons" International Journal of Molecular Sciences 22, no. 22: 12373. https://doi.org/10.3390/ijms222212373