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A current approach to wound healing and skin regeneration: Stem cell exosome therapy

Year 2024, Volume: 63 Issue: 4, 635 - 643, 09.12.2024

Ayşegül Taşkıran Dilek Taşkıran

https://doi.org/10.19161/etd.1529743

Abstract

The wound healing process is a long and challenging one in clinical practice, with current treatments showing limited effects. The wound healing process is associated with cell migration and proliferation, remodeling of extracellular matrix and angiogenesis. Various risk factors, chronic inflammation, and certain diseases can lead to insufficient wound closure, resulting in scar formation that may lead to fibrosis. In recent years, there has been evidence suggesting that mesenchymal stem cells (MSCs) have significant therapeutic potential for wound healing and skin regeneration. However, the direct application of MSCs still confronts many difficulties. Interestingly, exosomes, identified as “granular vesicles” with a lipid bilayer membrane structure involving specific components from their source cells, may reveal as an perfect alternative to MSCs. Various studies in recent years have shown that exosomes derived from MSCs are useful for wound healing and skin regeneration. The mechanisms by which exosomes are effective in the wound healing process include relieving inflammation, promoting vascularization, and the proliferation of epithelial cells and fibroblasts. Therefore, the application of MSC-exosomes may be a promising alternative to cell therapy in the treatment of skin wounds. This review will present current literature on the role and mechanisms of MSC-exosomes in wound healing and skin regeneration and will elaborate on the clinical potential of MSC-exosomes.

Keywords

Wound healing skin regeneration mesenchymal stem cell exosome aging exosome therapy

Project Number

Yok

References

  • Sylakowski K, Bradshaw A, Wells A. Mesenchymal stem cell/multipotent stromal cell augmentation of wound healing: lessons from the physiology of matrix and hypoxia support. Am J Pathol 2020;190(7):1370-1381. doi:10.1016/j.ajpath.2020.03.017.
  • Taylor DA, Chacon-Alberty L, Sampaio LC, et al. Recommendations for nomenclature and definition of cell products intended for human cardiovascular use. Cardiovasc Res 2022;118(11):2428-2436. doi:10.1093/cvr/cvab270.
  • Saadh MJ, Ramírez-Coronel AA, Saini RS, et al. Advances in mesenchymal stem/stromal cell-based therapy and their extracellular vesicles for skin wound healing. Hum Cell 2023;36(4):1253-1264. doi:10.1007/s13577-023-00904-8.
  • Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther 2019;10:68. doi: 10.1186/s13287-019-1165-5.
  • Pomatto M, Gai C, Negro F et al (2021) 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;22:1–26. doi:10. 3390/ijms2 20838 51.
  • Hu JC, Zheng CX, Sui BD, Liu WJ, Jin Y. Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration. World J Stem Cells 2022;14(5):318-329. doi:10.4252/wjsc.v14.i5.318.
  • Ding JY, Chen MJ, Wu LF. et al. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges. Military Med Res 2023;10:36. doi:10.1186/s40779-023-00472-w.
  • Zhou C, Zhang B, Yang Y, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. Stem Cell Res Ther 2023;14(1):107. doi:10.1186/s13287-023-03345-0.
  • Li J, Liu Y, Zhang R, et al. Insights into the role of mesenchymal stem cells in cutaneous medical aesthetics: from basics to clinics. Stem Cell Res Ther 2024;15(1):169. doi:10.1186/s13287-024-03774-5.
  • Rani Raju N, Silina E, Stupin V, Manturova N, Chidambaram SB, Achar RR. Multifunctional and smart wound dressings-A review on recent research advancements in skin regenerative medicine. Pharmaceutics 2022;14(8). doi:10.3390/pharmaceutics14081574.
  • Nathan C. Points of control in inflammation. Nature. 2002;420(6917):846–852.
  • Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005;6(12):1191–1197. doi:10.1038/ni1276.
  • Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci 2016;73(20):3861–3885. doi: 10.1007/s00018-016-2268-0.
  • Chaudhary M, Khan A, Gupta M. Skin ageing: pathophysiology and current market treatment approaches. Curr Aging Sci 2020;13(1):22-30. doi:10.2174/1567205016666190809161115.
  • Qian H, Shan Y, Gong R, et al. Mechanism of action and therapeutic effects of oxidative stress and stem cell-based materials in skin aging: Current evidence and future perspectives. Front Bioeng Biotechnol 2023;10:1082403. doi:10.3389/fbioe.2022.1082403.
  • Quan T, Fisher GJ. Role of age-associated alterations of the dermal extracellular matrix microenvironment in human skin aging: a mini-review. Gerontology 2015;61(5):427-434. doi:10.1159/000371708.
  • Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 2020;59:101036. doi:10.1016/j.arr.2020.101036.
  • Wang Y, Wang L, Wen X, et al. NF-κB signaling in skin aging. Mech Ageing Dev 2019;184:111160. doi:10.1016/j.mad.2019.111160.
  • Kim M, Shibata T, Kwon S, Park TJ, Kang HY. Ultraviolet-irradiated endothelial cells secrete stem cell factor and induce epidermal pigmentation. Sci Rep 2018;8(1):4235. doi:10.1038/s41598-018-22608-y.
  • Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020;367:eaau6977.
  • Arbade G, Jose JV, Gulbake A. et al. From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine. Cytotechnology 2024;76,363–401. doi:10.1007/s10616-024-00631-4
  • Heo JS, Kim S, Yang CE, Choi Y, Song SY, Kim HO. Human adipose mesenchymal stem cell-derived exosomes: a key player in wound healing. Tissue Eng Regen Med 2021;18:537–48.
  • Xiong M, Zhang Q, Hu W, et al. The novel mechanisms and applications of exosomes in dermatology and cutaneous medical aesthetics. Pharmacol Res 2021;166:105490. doi:10.1016/j.phrs.2021.105490.
  • Ye H, Wang F, Xu G, Shu F, Fan K, Wang D. Advancements in engineered exosomes for wound repair: current research and future perspectives. Front Bioeng Biotechnol 2023;11:1301362. doi:10.3389/fbioe.2023.1301362.
  • Li M, Wang T, Tian H, Wei G, Zhao L, Shi Y. Macrophage-derived exosomes accelerate wound healing through their anti-inflammation effects in a diabetic rat model. Artif Cells Nanomed Biotechnol 2019;47(1):3793-3803. doi:10.1080/21691401.2019.1669617.
  • Li X, Liu L, Yang J, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates mir-181c attenuating burn-induced excessive inflammation. EBioMedicine 2016;8:72-82. doi:10.1016/j.ebiom.2016.04.030.
  • He X, Dong Z, Cao Y, et al. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells Int 2019;2019:7132708. doi:10.1155/2019/7132708.
  • Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E. Mesenchymal stem cell exosomes ınduce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev 2015;24:1635-1647. doi:10.1089/scd.2014.0316.
  • Zhang W, Bai X, Zhao B, Li Y, Zhang Y, Li Z, Wang X, Luo L, Han F, Zhang J, Han S, Cai W, Su L, Tao K, Shi J, Hu D. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Exp Cell Res 2018;370:333-342. doi:10.1016/j.yexcr.2018.06.035.
  • Ren S, Chen J, Duscher D, Liu Y, Guo G, Kang Y, Xiong H, Zhan P, Wang Y, Wang C, Machens HG, Chen Z. 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. doi:10.1186/s13287-019-1152-x.
  • Zhang Y, Pan Y, Liu Y, Li X, Tang L, Duan M, Li J, Zhang G. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition. Stem Cell Res Ther 2021;12:434. doi:10.1186/s13287-021-02517-0.
  • Zhou Y, Zhao B, Zhang X-L, Lu Y, Lu S-T, Cheng J, et al. Combined topical and systemic administration with human adipose-derived mesenchymal stem cells (hADSC) and hADSC-derived exosomes markedly promoted cutaneous wound healing and regeneration. Stem Cell Res Ther 2021;12:257.
  • Hu S, Li Z, Cores J, Huang K, Su T, Dinh PU, Cheng K. Needle-free injection of exosomes derived from human dermal fibroblast spheroids ameliorates skin photoaging. ACS Nano 2019;13(10): 11273–11282. doi:10.1021/acsnano.9b04384.
  • Kwon HH, Yang SH, Lee J, Park BC, Park KY, Jung JY, Bae Y, Park GH. Combination treatment with human adipose tissue stem cell-derived exosomes and fractional CO2 laser for acne scars: a 12-week prospective, double-blind, randomized, split-face study. Acta Derm Venereol 2020;100(18):adv00310. doi:10.2340/00015555-3666.
  • Pumford AD, Staricha KL, Kunkel ET, Armstrong MF, Behfar A, Van Abel KM. Exosome therapy for a nonhealing scalp wound following chemoradiation and surgical therapy. Mayo Clin Proc 2024;99(6):1006-1012. doi: 10.1016/j.mayocp.2024.04.011.
  • Peredo M, Shivananjappa S. Topical human mesenchymal stem cell-derived exosomes for acceleration of wound healing following tissue trauma and aesthetic procedures: a case series. J Drugs Dermatol 2024;23(4):281-284. doi:10.36849/JDD.C7395.
  • Proffer SL, Paradise CR, DeGrazia E, et al. Efficacy and tolerability of topical platelet exosomes for skin rejuvenation: six-week results. Aesthet Surg J 2022;42(10):1185-1193. doi:10.1093/asj/sjac149.
  • Park GH, Kwon HH, Seok J, et al. Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study. J Cosmet Dermatol 2023;22(12):3418-3426. doi:10.1111/jocd.15872.

Yara iyileşmesi ve cilt rejenerasyonuna güncel bir yaklaşım: Kök hücre eksozom tedavisi

Year 2024, Volume: 63 Issue: 4, 635 - 643, 09.12.2024

Ayşegül Taşkıran Dilek Taşkıran

https://doi.org/10.19161/etd.1529743

Abstract

Yara iyileşme süreci, klinik uygulamada birtakım zorluklarla seyreden uzun bir süreç olup güncel tedavilerin etkileri halen sınırlıdır. Yara iyileşme süreci, hücrelerin göçü ve proliferasyonu, ekstraselüler matriksin yeniden şekillendirilmesi ve anjiyogenez ile ilişkilidir. Çeşitli risk faktörleri, kronik iltihaplanma ve bazı hastalıklar, yetersiz yara kapanmasına yol açarak fibrozisle sonuçlanabilecek bir yara izi oluşmasına neden olabilir. Son yıllarda, mezenkimal kök hücrelerin (MKH) yara iyileşmesi ve cilt yenilenmesi üzerinde güçlü terapötik potansiyele sahip olduğuna dair kanıtlar ortaya çıkmıştır. Ancak, MKH'lerin doğrudan uygulanmasında hala birçok sorunla karşılaşılmaktadır. Bununla birlikte son yıllarda, köken aldığı hücrelerden belirli bileşenler içeren lipid çift tabakalı membran yapısına sahip ve “granüler veziküller” olarak tanımlanan eksozomlar, MKH'ler için mükemmel bir alternatif olarak ortaya çıkmıştır. Çeşitli çalışmalarda özellikle MKH'lerden türetilen eksozomların (MKHE) yaraların iyileşmesi ve cilt rejenerasyonu için faydalı olduğu gösterilmiştir. Eksozomların cilt yaralarını iyileştirme sürecinde etkili olduğu mekanizmalar arasında inflamasyonu hafifletmek, damar oluşumunu uyarmak, epitel hücreleri ve fibroblastların proliferasyon ve göçünü uyarmak yer almaktadır. Bu nedenle, MKHE uygulanması, cilt yaralarının tedavisinde hücre tedavisine umut verici bir alternatif olabilir ve aynı anda birden fazla mekanizma aracılığıyla yara iyileşmesini teşvik edebilir. Bu derlemede, MKH'lerden türetilen eksozomların yara iyileşmesinde ve cilt rejenerasyonundaki rolü ve mekanizmaları hakkında güncel bilgiler sunulacak ve MKHE’lerin klinik uygulamalardaki potansiyelleri ayrıntılı olarak ele alınacaktır.

Keywords

Yara iyileşmesi cilt rejenerasyonu mezenkimal kök hücre eksozom yaşlanma eksozom tedavisi

Ethical Statement

Yok

Supporting Institution

Yok

Project Number

Yok

Thanks

Yok

References

  • Sylakowski K, Bradshaw A, Wells A. Mesenchymal stem cell/multipotent stromal cell augmentation of wound healing: lessons from the physiology of matrix and hypoxia support. Am J Pathol 2020;190(7):1370-1381. doi:10.1016/j.ajpath.2020.03.017.
  • Taylor DA, Chacon-Alberty L, Sampaio LC, et al. Recommendations for nomenclature and definition of cell products intended for human cardiovascular use. Cardiovasc Res 2022;118(11):2428-2436. doi:10.1093/cvr/cvab270.
  • Saadh MJ, Ramírez-Coronel AA, Saini RS, et al. Advances in mesenchymal stem/stromal cell-based therapy and their extracellular vesicles for skin wound healing. Hum Cell 2023;36(4):1253-1264. doi:10.1007/s13577-023-00904-8.
  • Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther 2019;10:68. doi: 10.1186/s13287-019-1165-5.
  • Pomatto M, Gai C, Negro F et al (2021) 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;22:1–26. doi:10. 3390/ijms2 20838 51.
  • Hu JC, Zheng CX, Sui BD, Liu WJ, Jin Y. Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration. World J Stem Cells 2022;14(5):318-329. doi:10.4252/wjsc.v14.i5.318.
  • Ding JY, Chen MJ, Wu LF. et al. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges. Military Med Res 2023;10:36. doi:10.1186/s40779-023-00472-w.
  • Zhou C, Zhang B, Yang Y, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. Stem Cell Res Ther 2023;14(1):107. doi:10.1186/s13287-023-03345-0.
  • Li J, Liu Y, Zhang R, et al. Insights into the role of mesenchymal stem cells in cutaneous medical aesthetics: from basics to clinics. Stem Cell Res Ther 2024;15(1):169. doi:10.1186/s13287-024-03774-5.
  • Rani Raju N, Silina E, Stupin V, Manturova N, Chidambaram SB, Achar RR. Multifunctional and smart wound dressings-A review on recent research advancements in skin regenerative medicine. Pharmaceutics 2022;14(8). doi:10.3390/pharmaceutics14081574.
  • Nathan C. Points of control in inflammation. Nature. 2002;420(6917):846–852.
  • Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005;6(12):1191–1197. doi:10.1038/ni1276.
  • Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci 2016;73(20):3861–3885. doi: 10.1007/s00018-016-2268-0.
  • Chaudhary M, Khan A, Gupta M. Skin ageing: pathophysiology and current market treatment approaches. Curr Aging Sci 2020;13(1):22-30. doi:10.2174/1567205016666190809161115.
  • Qian H, Shan Y, Gong R, et al. Mechanism of action and therapeutic effects of oxidative stress and stem cell-based materials in skin aging: Current evidence and future perspectives. Front Bioeng Biotechnol 2023;10:1082403. doi:10.3389/fbioe.2022.1082403.
  • Quan T, Fisher GJ. Role of age-associated alterations of the dermal extracellular matrix microenvironment in human skin aging: a mini-review. Gerontology 2015;61(5):427-434. doi:10.1159/000371708.
  • Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 2020;59:101036. doi:10.1016/j.arr.2020.101036.
  • Wang Y, Wang L, Wen X, et al. NF-κB signaling in skin aging. Mech Ageing Dev 2019;184:111160. doi:10.1016/j.mad.2019.111160.
  • Kim M, Shibata T, Kwon S, Park TJ, Kang HY. Ultraviolet-irradiated endothelial cells secrete stem cell factor and induce epidermal pigmentation. Sci Rep 2018;8(1):4235. doi:10.1038/s41598-018-22608-y.
  • Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020;367:eaau6977.
  • Arbade G, Jose JV, Gulbake A. et al. From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine. Cytotechnology 2024;76,363–401. doi:10.1007/s10616-024-00631-4
  • Heo JS, Kim S, Yang CE, Choi Y, Song SY, Kim HO. Human adipose mesenchymal stem cell-derived exosomes: a key player in wound healing. Tissue Eng Regen Med 2021;18:537–48.
  • Xiong M, Zhang Q, Hu W, et al. The novel mechanisms and applications of exosomes in dermatology and cutaneous medical aesthetics. Pharmacol Res 2021;166:105490. doi:10.1016/j.phrs.2021.105490.
  • Ye H, Wang F, Xu G, Shu F, Fan K, Wang D. Advancements in engineered exosomes for wound repair: current research and future perspectives. Front Bioeng Biotechnol 2023;11:1301362. doi:10.3389/fbioe.2023.1301362.
  • Li M, Wang T, Tian H, Wei G, Zhao L, Shi Y. Macrophage-derived exosomes accelerate wound healing through their anti-inflammation effects in a diabetic rat model. Artif Cells Nanomed Biotechnol 2019;47(1):3793-3803. doi:10.1080/21691401.2019.1669617.
  • Li X, Liu L, Yang J, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates mir-181c attenuating burn-induced excessive inflammation. EBioMedicine 2016;8:72-82. doi:10.1016/j.ebiom.2016.04.030.
  • He X, Dong Z, Cao Y, et al. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells Int 2019;2019:7132708. doi:10.1155/2019/7132708.
  • Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E. Mesenchymal stem cell exosomes ınduce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev 2015;24:1635-1647. doi:10.1089/scd.2014.0316.
  • Zhang W, Bai X, Zhao B, Li Y, Zhang Y, Li Z, Wang X, Luo L, Han F, Zhang J, Han S, Cai W, Su L, Tao K, Shi J, Hu D. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Exp Cell Res 2018;370:333-342. doi:10.1016/j.yexcr.2018.06.035.
  • Ren S, Chen J, Duscher D, Liu Y, Guo G, Kang Y, Xiong H, Zhan P, Wang Y, Wang C, Machens HG, Chen Z. 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. doi:10.1186/s13287-019-1152-x.
  • Zhang Y, Pan Y, Liu Y, Li X, Tang L, Duan M, Li J, Zhang G. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition. Stem Cell Res Ther 2021;12:434. doi:10.1186/s13287-021-02517-0.
  • Zhou Y, Zhao B, Zhang X-L, Lu Y, Lu S-T, Cheng J, et al. Combined topical and systemic administration with human adipose-derived mesenchymal stem cells (hADSC) and hADSC-derived exosomes markedly promoted cutaneous wound healing and regeneration. Stem Cell Res Ther 2021;12:257.
  • Hu S, Li Z, Cores J, Huang K, Su T, Dinh PU, Cheng K. Needle-free injection of exosomes derived from human dermal fibroblast spheroids ameliorates skin photoaging. ACS Nano 2019;13(10): 11273–11282. doi:10.1021/acsnano.9b04384.
  • Kwon HH, Yang SH, Lee J, Park BC, Park KY, Jung JY, Bae Y, Park GH. Combination treatment with human adipose tissue stem cell-derived exosomes and fractional CO2 laser for acne scars: a 12-week prospective, double-blind, randomized, split-face study. Acta Derm Venereol 2020;100(18):adv00310. doi:10.2340/00015555-3666.
  • Pumford AD, Staricha KL, Kunkel ET, Armstrong MF, Behfar A, Van Abel KM. Exosome therapy for a nonhealing scalp wound following chemoradiation and surgical therapy. Mayo Clin Proc 2024;99(6):1006-1012. doi: 10.1016/j.mayocp.2024.04.011.
  • Peredo M, Shivananjappa S. Topical human mesenchymal stem cell-derived exosomes for acceleration of wound healing following tissue trauma and aesthetic procedures: a case series. J Drugs Dermatol 2024;23(4):281-284. doi:10.36849/JDD.C7395.
  • Proffer SL, Paradise CR, DeGrazia E, et al. Efficacy and tolerability of topical platelet exosomes for skin rejuvenation: six-week results. Aesthet Surg J 2022;42(10):1185-1193. doi:10.1093/asj/sjac149.
  • Park GH, Kwon HH, Seok J, et al. Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study. J Cosmet Dermatol 2023;22(12):3418-3426. doi:10.1111/jocd.15872.
There are 38 citations in total.

Details

Primary Language Turkish
Subjects Medical Physiology (Other)
Journal Section Reviews
Authors

Ayşegül Taşkıran 0009-0007-6160-6566

Dilek Taşkıran 0000-0002-4505-0939

Project Number Yok
Publication Date December 9, 2024
Submission Date August 7, 2024
Acceptance Date August 25, 2024
Published in Issue Year 2024Volume: 63 Issue: 4

Cite

Vancouver Taşkıran A, Taşkıran D. Yara iyileşmesi ve cilt rejenerasyonuna güncel bir yaklaşım: Kök hücre eksozom tedavisi. EJM. 2024;63(4):635-43.
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