{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:55:36Z","timestamp":1790787336938,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns. This review provides an overview of the pathophysiology of cutaneous wounds and the potential of MSCs-based cell-free therapy in each phase of wound healing. It also discusses clinical studies of MSCs-based cell-free therapies.<\/jats:p>","DOI":"10.3390\/ijms24119356","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:19:37Z","timestamp":1685204377000},"page":"9356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["The Potential of MSC-Based Cell-Free Therapy in Wound Healing\u2014A Thorough Literature Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-597X","authenticated-orcid":false,"given":"Hui","family":"Ma","sequence":"first","affiliation":[{"name":"Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"},{"name":"State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2791-7121","authenticated-orcid":false,"given":"Wing-Sum","family":"Siu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"},{"name":"State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-4688","authenticated-orcid":false,"given":"Ping-Chung","family":"Leung","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"},{"name":"State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1111\/j.1365-4632.2011.04940.x","article-title":"Wound healing in adult skin: Aiming for perfect regeneration","volume":"50","author":"Heng","year":"2011","journal-title":"Int. J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000339613","article-title":"Wound repair and regeneration","volume":"49","author":"Reinke","year":"2012","journal-title":"Eur. Surg. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1089\/ten.teb.2018.0350","article-title":"Regenerative Scar-Free Skin Wound Healing","volume":"25","author":"Monavarian","year":"2019","journal-title":"Tissue Eng."},{"key":"ref_4","unstructured":"Ozgok Kangal, M.K., and Regan, J.P. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F1000 Faculty Rev-787","DOI":"10.12688\/f1000research.18293.1","article-title":"Toward understanding scarless skin wound healing and pathological scarring","volume":"8","author":"Karppinen","year":"2019","journal-title":"F1000Research"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Raziyeva, K., Kim, Y., Zharkinbekov, Z., Kassymbek, K., Jimi, S., and Saparov, A. (2021). Immunology of Acute and Chronic Wound Healing. Biomolecules, 11.","DOI":"10.3390\/biom11050700"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1468-3083.2010.03775.x","article-title":"Management of minor acute cutaneous wounds: Importance of wound healing in a moist environment","volume":"25","author":"Korting","year":"2011","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.clindermatol.2021.10.002","article-title":"Nutrition and cutaneous wound healing","volume":"40","author":"Grada","year":"2022","journal-title":"Clin. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13643-016-0329-y","article-title":"Prevalence and incidence of chronic wounds and related complications: A protocol for a systematic review","volume":"5","author":"Ni","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1160\/TH06-11-0625","article-title":"Clinical implications of gene polymorphisms in venous leg ulcer: A model in tissue injury and reparative process","volume":"98","author":"Zamboni","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_11","first-page":"159","article-title":"Chronic Wounds: Evaluation and Management","volume":"101","author":"Bowers","year":"2020","journal-title":"Am. Fam. Physician"},{"key":"ref_12","unstructured":"Nagle, S.M., Stevens, K.A., and Wilbraham, S.C. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1152\/physrev.00067.2017","article-title":"Wound healing: A cellular perspective","volume":"99","author":"Rodrigues","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., and Conti, B. (2020). Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080735"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s13671-018-0234-9","article-title":"Immunology of wound healing","volume":"7","author":"Ellis","year":"2018","journal-title":"Curr. Dermatol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.blre.2014.10.003","article-title":"Platelet secretion: From haemostasis to wound healing and beyond","volume":"29","author":"Golebiewska","year":"2015","journal-title":"Blood Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200223","DOI":"10.1098\/rsob.200223","article-title":"Wound healing: Cellular mechanisms and pathological outcomes","volume":"10","author":"Wilkinson","year":"2020","journal-title":"Open. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.thromres.2019.05.001","article-title":"Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing","volume":"179","author":"Opneja","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_19","first-page":"146764","article-title":"Complements and the wound healing cascade: An updated review","volume":"2013","author":"Sinno","year":"2013","journal-title":"Plast. Surg. Int."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hassanshahi, A., Moradzad, M., Ghalamkari, S., Fadaei, M., Cowin, A.J., and Hassanshahi, M. (2022). Macrophage-Mediated Inflammation in Skin Wound Healing. Cells, 11.","DOI":"10.3390\/cells11192953"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2503950","DOI":"10.1155\/2018\/2503950","article-title":"Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair","volume":"2018","author":"Silva","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/s41419-021-04294-3","article-title":"The emerging roles of neutrophil extracellular traps in wound healing","volume":"12","author":"Zhu","year":"2021","journal-title":"Cell. Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.it.2019.05.001","article-title":"The Healing Power of Neutrophils","volume":"40","author":"Phillipson","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_24","first-page":"109","article-title":"Macrophage polarization and diabetic wound healing","volume":"236","author":"Louiselle","year":"2021","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lopez, T., Wendremaire, M., Lagarde, J., Duquet, O., Alibert, L., Paquette, B., Garrido, C., and Lirussi, F. (2022). Wound Healing versus Metastasis: Role of Oxidative Stress. Biomedicines, 10.","DOI":"10.20944\/preprints202209.0354.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s11154-019-09492-1","article-title":"Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review","volume":"20","author":"Zubair","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.matbio.2018.01.002","article-title":"Extracellular matrix contribution to skin wound re-epithelialization","volume":"75\u201376","author":"Rousselle","year":"2019","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1083\/jcb.122.2.417","article-title":"Mutual induction of growth factor gene expression in by epidermal-dermal cell interaction","volume":"122","author":"Smola","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Piipponen, M., Li, D., and Land\u00e9n, N.X. (2020). The Immune Functions of Keratinocytes in Skin Wound Healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228790"},{"key":"ref_30","first-page":"421","article-title":"Stem cell-mediated angiogenesis in skin tissue engineering and wound healing","volume":"30","author":"Azari","year":"2022","journal-title":"Wound Rep. Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Rep. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.addr.2018.09.010","article-title":"Therapeutic strategies for enhancing angiogenesis in wound healing","volume":"146","author":"Veith","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.stem.2022.07.006","article-title":"Wound healing, fibroblast heterogeneity, and fibrosis","volume":"29","author":"Talbott","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1016\/j.biomaterials.2011.02.027","article-title":"The role of ECM proteins and protein fragments in guiding cell behavior in regenerative medicine","volume":"32","author":"Barker","year":"2011","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1755-1536-3-4","article-title":"Cell-matrix interactions in dermal repair and scarring","volume":"3","author":"Eckes","year":"2010","journal-title":"Fibrogenes. Tissue Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"El Ayadi, A., Jay, J.W., and Prasai, A. (2020). Current Approaches Targeting the Wound Healing Phases to Attenuate Fibrosis and Scarring. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031105"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"120096","DOI":"10.1016\/j.lfs.2021.120096","article-title":"Collagen-based formulations for wound healing: A literature review","volume":"290","author":"Sharma","year":"2022","journal-title":"Life Sci."},{"key":"ref_37","first-page":"4391","article-title":"Role of matrix metalloproteinase in wound healing","volume":"14","author":"Kandhwal","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.2337\/dc11-0807","article-title":"Location, location, location: Geographic clustering of lower-extremity amputation among Medicare beneficiaries with diabetes","volume":"34","author":"Margolis","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.12968\/jowc.2021.30.Sup9.S8","article-title":"Early wound bed preparation: Irrigation and debridement","volume":"30","author":"Stiehl","year":"2021","journal-title":"J. Wound Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/SLA.0000000000005786","article-title":"Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation On The Incidence Of Surgical Site Infection In Clean-Contaminated Wounds After Gastroenterological Surgery: A Single Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial","volume":"277","author":"Maemoto","year":"2022","journal-title":"Ann. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rai, S., Gupta, T.P., Shaki, O., and Kale, A. (2021). Hydrogen Peroxide: Its Use in an Extensive Acute Wound to Promote Wound Granulation and Infection Control\u2014Is it Better Than Normal Saline?. Int. J. Low. Extrem. Wounds, 15347346211032555.","DOI":"10.1177\/15347346211032555"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jaad.2015.08.070","article-title":"Wound healing and treating wounds: Chronic wound care and management","volume":"74","author":"Powers","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_43","first-page":"50","article-title":"Principles of Wound Dressings: A Review","volume":"35","author":"Obagi","year":"2019","journal-title":"Surg. Technol. Int."},{"key":"ref_44","unstructured":"Braza, M.E., and Fahrenkopf, M.P. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Holl, J., Kowalewski, C., Zimek, Z., Fiedor, P., Kaminski, A., Oldak, T., Moniuszko, M., and Eljaszewicz, A. (2021). Chronic Diabetic Wounds and Their Treatment with Skin Substitutes. Cells, 10.","DOI":"10.3390\/cells10030655"},{"key":"ref_46","first-page":"1","article-title":"The Effect of Aloe Vera Clinical Trials on Prevention and Healing of Skin Wound: A Systematic Review","volume":"44","author":"Hekmatpou","year":"2019","journal-title":"Iran. J. Med. Sci."},{"key":"ref_47","first-page":"152996","article-title":"Therapeutic potential of Aloe vera-A miracle gift of nature","volume":"60","author":"Kumar","year":"2019","journal-title":"Phytomed. Int. J. Phytother. Phytopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/pmic.201300547","article-title":"Comprehensive proteomic analysis of a Chinese 2-herb formula (Astragali Radix and Rehmanniae Radix) on mature endothelial cells","volume":"14","author":"Tam","year":"2014","journal-title":"Proteomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/1753-0407.12230","article-title":"Enumeration and functional investigation of endothelial progenitor cells in neovascularization of diabetic foot ulcer rats with a Chinese 2-herb formula","volume":"7","author":"Tam","year":"2015","journal-title":"J. Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/1753-0407.12117","article-title":"Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: A randomized double-blind placebo-controlled study","volume":"6","author":"Ko","year":"2014","journal-title":"J. Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1007\/s00018-019-03125-1","article-title":"Biological functions of mesenchymal stem cells and clinical implications","volume":"76","author":"Naji","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2019.04.002","article-title":"The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine","volume":"46","author":"Kumar","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mishra, V.K., Shih, H.H., Parveen, F., Lenzen, D., Ito, E., Chan, T.F., and Ke, L.Y. (2020). Identifying the Therapeutic Significance of Mesenchymal Stem Cells. Cells, 6.","DOI":"10.3390\/cells9051145"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1111\/cas.14563","article-title":"Biology and therapeutic potential of mesenchymal stem cell-derived exosomes","volume":"111","author":"Xunian","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mazini, L., Rochette, L., Admou, B., Amal, S., and Malka, G. (2020). Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041306"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1096\/fj.05-5211com","article-title":"Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement","volume":"20","author":"Gnecchi","year":"2006","journal-title":"FASEB J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"753","DOI":"10.2147\/CCID.S298105","article-title":"Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model\u2014A Preliminary Study","volume":"14","author":"Ma","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Stojanovi\u0107, S., and Najman, S. (2019). The Effect of Conditioned Media of Stem Cells Derived from Lipoma and Adipose Tissue on Macrophages\u2019 Response and Wound Healing in Indirect Co-culture System In Vitro. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071671"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/s13287-020-01819-z","article-title":"Human multipotent adult progenitor cell-conditioned medium improves wound healing through modulating inflammation and angiogenesis in mice","volume":"11","author":"Ahangar","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"954682","DOI":"10.3389\/fbioe.2022.954682","article-title":"Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications","volume":"10","author":"Kim","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ma, H., Siu, W.S., Koon, C.M., Wu, X.X., Li, X., Cheng, W., Shum, W.T., Lau, C.B., Wong, C.K., and Leung, P.C. (2023). The Application of Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and a Twin-Herb Formula to the Rodent Wound Healing Model: Use Alone or Together?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021372"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ahangar, P., Mills, S.J., and Cowin, A.J. (2020). Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197038"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.3389\/fimmu.2018.02837","article-title":"Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning","volume":"9","author":"Ferreira","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_65","first-page":"4951820","article-title":"Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41536-019-0070-y","article-title":"Proteomic analysis of human mesenchymal stromal cell secretomes: A systematic comparison of the angiogenic potential","volume":"4","author":"Kehl","year":"2019","journal-title":"NPJ Regen. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4356359","DOI":"10.1155\/2020\/4356359","article-title":"Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis","volume":"2020","author":"Maacha","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1089\/scd.2011.0674","article-title":"Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue","volume":"21","author":"Hsiao","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Guillamat-Prats, R. (2021). The Role of MSC in Wound Healing, Scarring and Regeneration. Cells, 10.","DOI":"10.3390\/cells10071729"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00403-019-02016-6","article-title":"Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors","volume":"312","author":"Saheli","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Campanella, C., Caruso Bavisotto, C., Logozzi, M., Marino Gammazza, A., Mizzoni, D., Cappello, F., and Fais, S. (2019). On the Choice of the Extracellular Vesicles for Therapeutic Purposes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020236"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(83)90040-5","article-title":"Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor","volume":"33","author":"Pan","year":"1983","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1042\/BST20180079","article-title":"MSC exosome works through a protein-based mechanism of action","volume":"46","author":"Toh","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"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","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_75","first-page":"77","article-title":"Bone marrow-derived mesenchymal stromal cell: What next?","volume":"11","author":"Borges","year":"2018","journal-title":"Stem Cells Cloning"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3389\/fimmu.2014.00556","article-title":"Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells","volume":"5","author":"Blazquez","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/term.2799","article-title":"Promising effects of exosomes isolated from menstrual blood-derived mesenchymal stem cell on wound-healing process in diabetic mouse model","volume":"13","author":"Dalirfardouei","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"384","DOI":"10.23736\/S0026-4806.20.07205-5","article-title":"Stem cell-derived exosomes for wound healing: Current status and promising directions","volume":"112","author":"Vu","year":"2021","journal-title":"Minerva Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7132708","DOI":"10.1155\/2019\/7132708","article-title":"MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing","volume":"2019","author":"He","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12967-015-0642-6","article-title":"LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b","volume":"13","author":"Ti","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ebiom.2016.04.030","article-title":"Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation","volume":"8","author":"Li","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"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., and Sung, S. (2020). Mesenchymal Stem\/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells, 9.","DOI":"10.3390\/cells9051157"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1089\/scd.2014.0316","article-title":"Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro","volume":"24","author":"Shabbir","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/stem.1771","article-title":"HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing","volume":"33","author":"Zhang","year":"2015","journal-title":"Stem Cells"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"108259","DOI":"10.1016\/j.abb.2020.108259","article-title":"Highly-expressed micoRNA-21 in adipose derived stem cell exosomes can enhance the migration and proliferation of the HaCaT cells by increasing the MMP-9 expression through the PI3K\/AKT pathway","volume":"681","author":"Yang","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e22881","DOI":"10.1002\/jbt.22881","article-title":"Exosomes derived from ADSCs containing miR-378 promotes wound healing by targeting caspase-3","volume":"35","author":"Zheng","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2147\/CCID.S274370","article-title":"Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal microRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1\/TGF-\u03b2 Signaling Axis","volume":"13","author":"Cao","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"627","DOI":"10.2217\/rme-2021-0170","article-title":"LncRNA MALAT1 from human adipose-derived stem cell exosomes accelerates wound healing via miR-378a\/FGF2 axis","volume":"17","author":"Pi","year":"2022","journal-title":"Regen. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13287-019-1152-x","article-title":"Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways","volume":"10","author":"Ren","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1186\/s13287-019-1472-x","article-title":"Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells","volume":"10","author":"Yang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9742765","DOI":"10.1155\/2019\/9742765","article-title":"Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis","volume":"2019","author":"Ding","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/s12967-022-03479-4","article-title":"Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin","volume":"20","author":"Lintel","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1186\/s13287-021-02517-0","article-title":"Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-\u03b2 receptor inhibition","volume":"12","author":"Zhang","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102660","DOI":"10.1016\/j.jaut.2021.102660","article-title":"Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p","volume":"121","author":"Rozier","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Oualla-Bachiri, W., Fern\u00e1ndez-Gonz\u00e1lez, A., Qui\u00f1ones-Vico, M.I., and Arias-Santiago, S. (2020). From Grafts to Human Bioengineered Vascularized Skin Substitutes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218197"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1038\/s41598-018-27568-x","article-title":"Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery","volume":"8","author":"Wahlberg","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s12015-018-9817-x","article-title":"Mesenchymal Stem Cells on Horizon: A New Arsenal of Therapeutic Agents","volume":"14","author":"Roushandeh","year":"2018","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.32604\/biocell.2022.019591","article-title":"Production of mesenchymal stem cell derived-secretome as cell-free regenerative therapy and immunomodulation: A biomanufacturing perspective","volume":"46","author":"Torizal","year":"2022","journal-title":"Biocell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/1673-5374.264455","article-title":"Mesenchymal stem cells secretome: Current trends and future challenges","volume":"15","author":"Teixeira","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Sagaradze, G., Grigorieva, O., Nimiritsky, P., Basalova, N., Kalinina, N., Akopyan, Z., and Efimenko, A. (2019). Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071656"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cryobiol.2018.02.008","article-title":"Fetal bovine serum-free cryopreservation methods for clinical banking of human adipose-derived stem cells","volume":"81","author":"Park","year":"2018","journal-title":"Cryobiology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:43:19Z","timestamp":1760125399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,27]]},"references-count":101,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119356"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119356","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,27]]}}}