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The Mechanisms of Adipose Stem Cell-Derived Exosomes Promote Wound Healing and Regeneration

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Abstract

Chronic wound healing is a class of diseases influenced by multiple complex factors, causing severe psychological and physiological impact on patients. It is an intractable clinical challenge and its possible mechanisms are not yet clear. It has been proven that adipose stem cell-derived exosomes (ADSC-Exos) can promote wound healing and inhibit scar formation by regulating inflammation, promoting cell proliferation, migration, and angiogenesis, regulating matrix remodeling, which provides a new approach for wound healing through biological treatment. This review focuses on the mechanism, treatment, and administration methods of ADSC-Exos in wound healing, providing a comprehensive understanding the mechanisms of ADSC-Exos on wound healing.

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Reference

  1. Ko KI, Sculean A, Graves DT (2021) Diabetic wound healing in soft and hard oral tissues. Transl Res 236:72–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Alma A et al (2023) Obesity and wound healing: focus on mesenchymal stem cells. Life (Basel). https://doi.org/10.3390/life13030717

    Article  PubMed  Google Scholar 

  3. Zhu S et al (2021) The emerging roles of neutrophil extracellular traps in wound healing. Cell Death Dis 12(11):984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burgess JL et al (2021) Diabetic wound-healing science. Medicina (Kaunas) 57(10):1072

    Article  PubMed  Google Scholar 

  5. Yang S et al (2022) Pathogenesis and treatment of wound healing in patients with diabetes after tooth extraction. Front Endocrinol (Lausanne) 13:949535

    Article  PubMed  Google Scholar 

  6. Baharlouei P, Rahman A (2022) Chitin and chitosan: prospective biomedical applications in drug delivery, cancer treatment, and wound healing. Mar Drugs 20(7):460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wani SUD et al (2022) Silk fibroin as an efficient biomaterial for drug delivery, gene therapy, and wound healing. Int J Mol Sci 23(22):14421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hao M et al (2022) Engineered stem cell exosomes for oral and maxillofacial wound healing. Front Bioeng Biotechnol 10:1038261

    Article  PubMed  PubMed Central  Google Scholar 

  9. Huang C et al (2022) Anti-inflammatory hydrogel dressings and skin wound healing. Clin Transl Med 12(11):e1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li S et al (2023) Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells(ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin. Biomater Res 27(1):11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Legrand JMD, Martino MM (2022) Growth factor and cytokine delivery systems for wound healing. Cold Spring Harb Perspect Biol 14(8):a041234

    Article  CAS  PubMed  Google Scholar 

  12. Zhang M et al (2023) Advances in 3D skin bioprinting for wound healing and disease modeling. Regen Biomater 10:rbac105

    Article  CAS  PubMed  Google Scholar 

  13. Zhang B et al (2022) Adipose-derived stem cell conditioned medium and wound healing: a systematic review. Tissue Eng Part B Rev 28(4):830–847

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  14. Xu ZH et al (2023) Progress and expectation of stem cell therapy for diabetic wound healing. World J Clin Cases 11(3):506–513

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kallmeyer K et al (2020) Fate of systemically and locally administered adipose-derived mesenchymal stromal cells and their effect on wound healing. Stem Cells Transl Med 9(1):131–144

    Article  CAS  PubMed  Google Scholar 

  16. Schneider I, Calcagni M, Buschmann J (2023) Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review. Cytotherapy 25(2):105–119

    Article  CAS  PubMed  Google Scholar 

  17. Xie F et al (2022) Interleukin-10-modified adipose-derived mesenchymal stem cells prevent hypertrophic scar formation via regulating the biological characteristics of fibroblasts and inflammation. Mediators Inflamm 2022:6368311

    Article  PubMed  PubMed Central  Google Scholar 

  18. Long C et al (2022) Therapeutic potential of exosomes from adipose-derived stem cells in chronic wound healing. Front Surg 9:1030288

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhou Y et al (2022) Human adipose-derived mesenchymal stem cells-derived exosomes encapsulated in pluronic F127 hydrogel promote wound healing and regeneration. Stem Cell Res Ther 13(1):407

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ren S et al (2022) Exosomes from adipose stem cells promote diabetic wound healing through the eHSP90/LRP1/AKT axis. Cells 11(20):3229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. He L et al (2020) ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway. Biosci Rep 40(5):BSR20192549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ju Y et al (2023) Extracellular vesicle-loaded hydrogels for tissue repair and regeneration. Mater Today Bio 18:100522

    Article  CAS  PubMed  Google Scholar 

  23. Su X, Wang T, Guo S (2021) Applications of 3D printed bone tissue engineering scaffolds in the stem cell field. Regen Ther 16:63–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen S et al (2019) Exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells promote bone regeneration. Cell Prolif 52(5):e12669

    Article  PubMed  PubMed Central  Google Scholar 

  25. Heo JS, Kim S (2022) Human adipose mesenchymal stem cells modulate inflammation and angiogenesis through exosomes. Sci Rep 12(1):2776

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ge L et al (2023) Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction. Front Bioeng Biotechnol 11:1129538

    Article  PubMed  PubMed Central  Google Scholar 

  27. Liu K et al (2019) Adipose stem cell-derived exosomes in combination with hyaluronic acid accelerate wound healing through enhancing re-epithelialization and vascularization. Br J Dermatol 181(4):854–856

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  28. Ma J et al (2022) Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing. J Mater Chem B 10(46):9565–9577

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  29. Ludwig N, Whiteside TL, Reichert TE (2019) Challenges in exosome isolation and analysis in health and disease. Int J Mol Sci 20(19):4684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li P et al (2017) Progress in exosome isolation techniques. Theranostics 7(3):789–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vella LJ et al (2017) A rigorous method to enrich for exosomes from brain tissue. J Extracell Vesicles 6(1):1348885

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wu CX, Liu ZF (2018) Proteomic profiling of sweat exosome suggests its involvement in skin immunity. J Invest Dermatol 138(1):89–97

    Article  CAS  PubMed  Google Scholar 

  33. van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19(4):213–228

    Article  PubMed  Google Scholar 

  34. Shen Q et al (2022) Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease. J Adv Res 37:221–233

    Article  CAS  PubMed  Google Scholar 

  35. Bugg D et al (2022) MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing. Cell Stem Cell 29(3):419-433.e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mahmoudi S et al (2019) Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing. Nature 574(7779):553–558

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Venugopal H et al (2022) Properties and functions of fibroblasts and myofibroblasts in myocardial infarction. Cells 11(9):1386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Andugulapati SB et al (2020) Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems. Phytomedicine 78:153298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mölzer C et al (2019) TGF-β1-activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full-thickness hydrogel transplantation. J Tissue Eng Regen Med 13(9):1507–1517

    Article  PubMed  Google Scholar 

  40. Ibrahim Al-Mashahedah AM, Kanwar RK, Kanwar JR (2019) Utility of nanomedicine targeting scar-forming myofibroblasts to attenuate corneal scarring and haze. Nanomedicine (Lond) 14(8):1049–1072

    Article  CAS  PubMed  Google Scholar 

  41. Tutuianu R et al (2021) Human mesenchymal stromal cell-derived exosomes promote in vitro wound healing by modulating the biological properties of skin keratinocytes and fibroblasts and stimulating angiogenesis. Int J Mol Sci 22(12):6239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang J et al (2021) Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways. J Nanobiotechnol 19(1):202

    Article  CAS  Google Scholar 

  43. Li L et al (2019) Conditioned medium from human adipose-derived mesenchymal stem cell culture prevents UVB-induced skin aging in human keratinocytes and dermal fibroblasts. Int J Mol Sci 21(1):49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Han X et al (2021) Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway. Cell Cycle 20(5–6):616–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang Y et al (2022) Attenuation of hepatic ischemia-reperfusion injury by adipose stem cell-derived exosome treatment via ERK1/2 and GSK-3β signaling pathways. Int J Mol Med 49(2):1–2

    Google Scholar 

  46. Qian L et al (2021) Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis. Lab Invest 101(9):1254–1266

    Article  CAS  PubMed  Google Scholar 

  47. Li C et al (2022) Application of ADSCs and their exosomes in scar prevention. Stem Cell Rev Rep 18(3):952–967

    Article  PubMed  Google Scholar 

  48. Lv Q et al (2020) Engineered human adipose stem-cell-derived exosomes loaded with miR-21-5p to promote diabetic cutaneous wound healing. Mol Pharm 17(5):1723–1733

    Article  ADS  MathSciNet  CAS  PubMed  Google Scholar 

  49. Nguyen TH, Pham PV, Vu NB (2023) Exosomes from adipose-derived stem cells promote angiogenesis and reduce necrotic grade in hindlimb ischemia mouse models. Iran J Basic Med Sci 26(4):429–437

    PubMed  PubMed Central  Google Scholar 

  50. Bai Y et al (2018) Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem Biophys Res Commun 500(2):310–317

    Article  CAS  PubMed  Google Scholar 

  51. Chen K et al (2022) Adipose-derived stem cells exosomes improve fat graft survival by promoting prolipogenetic abilities through wnt/β-catenin pathway. Stem Cells Int 2022:5014895

    Article  PubMed  PubMed Central  Google Scholar 

  52. Han Y et al (2019) Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R. Int J Biochem Cell Biol 109:59–68

    Article  CAS  PubMed  Google Scholar 

  53. Zhang W et al (2018) Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Exp Cell Res 370(2):333–342

    Article  ADS  CAS  PubMed  Google Scholar 

  54. Shi R et al (2020) Exosomes derived from mmu_circ_0000250-modified adipose-derived mesenchymal stem cells promote wound healing in diabetic mice by inducing miR-128-3p/SIRT1-mediated autophagy. Am J Physiol Cell Physiol 318(5):C848-c856

    Article  CAS  PubMed  Google Scholar 

  55. Xu F et al (2019) Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu. Stem Cell Res Ther 10(1):106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yang Y et al (2018) Exosomes secreted by adipose-derived stem cells contribute to angiogenesis of brain microvascular endothelial cells following oxygen-glucose deprivation in vitro through microRNA-181b/TRPM7 axis. J Mol Neurosci 65(1):74–83

    Article  CAS  PubMed  Google Scholar 

  57. Du L et al (2018) Exosomes from microRNA-199-3p-modified adipose-derived stem cells promote proliferation and migration of endothelial tip cells by downregulation of semaphorin 3A. Int J Clin Exp Pathol 11(10):4879–4888

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Aitcheson SM et al (2021) Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds. Molecules 26(16):4917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schmitt H et al (2020) The TLR9 agonist cobitolimod induces IL10-producing wound healing macrophages and regulatory T Cells in ulcerative colitis. J Crohns Colitis 14(4):508–524

    Article  PubMed  Google Scholar 

  60. Chen B et al (2021) Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg(2+)/curcumin from injectable self-healing hydrogels. Theranostics 11(12):5911–5925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Short WD, Wang X, Keswani SG (2022) The role of T lymphocytes in cutaneous scarring. Adv Wound Care (New Rochelle) 11(3):121–131

    Article  PubMed  Google Scholar 

  62. Chen H et al (2017) Mast cell chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating TGF-β1/Smads signaling pathway. Exp Ther Med 14(5):4438–4442

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Yang WZ et al (2007) Effects of low power laser irradiation on intracellular calcium and histamine release in RBL-2H3 mast cells. Photochem Photobiol 83(4):979–984

    Article  CAS  PubMed  Google Scholar 

  64. Yang M et al (2023) Analysis of curative effect of insulin external application on burn wounds of diabetic patients with different depths. Int Wound J 20(5):1393–1401

    Article  PubMed  Google Scholar 

  65. Kieran I et al (2013) Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies. Wound Repair Regen 21(3):428–436

    Article  PubMed  Google Scholar 

  66. Huang S et al (2021) Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. Cell Stem Cell 28(9):1582-1596.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li C et al (2022) Adipose mesenchymal stem cell-derived exosomes promote wound healing through the WNT/β-catenin signaling pathway in dermal fibroblasts. Stem Cell Rev Rep 18(6):2059–2073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hu L et al (2016) Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep 6:32993

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ma T et al (2019) Adipose mesenchymal stem cell-derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β-catenin signaling in cutaneous wound healing. J Cell Biochem 120(6):10847–10854

    Article  CAS  PubMed  Google Scholar 

  70. Yang C et al (2020) 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. Arch Biochem Biophys 681:108259

    Article  CAS  PubMed  Google Scholar 

  71. Zhang G, Song K, Yan H (2019) MicroRNA-124 represses wound healing by targeting SERP1 and inhibiting the Wnt/β-catenin pathway. Adv Clin Exp Med 28(6):711–718

    Article  PubMed  Google Scholar 

  72. Meng X et al (2021) Umbilical cord-derived mesenchymal stem cells exert anti-fibrotic action on hypertrophic scar-derived fibroblasts in co-culture by inhibiting the activation of the TGF β1/Smad3 pathway. Exp Ther Med 21(3):210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. DiPietro LA (2016) Angiogenesis and wound repair: when enough is enough. J Leukoc Biol 100(5):979–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wang L et al (2021) Author correction: exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. Sci Rep 11(1):3245

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  75. Qu Y et al (2017) Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 21(10):2491–2502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Fang S et al (2016) Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-β/SMAD2 pathway during wound healing. Stem Cells Transl Med 5(10):1425–1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Zhengjie Lin and Danyi Lin are contributed equally to this work.

Authors and Affiliations

  1. Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China

    Zhengjie Lin

  2. Department of Pathology, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, China

    Danyi Lin

  3. Neonatal Intensive Care Unit, Department of Pediatrics, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou, Guangdong, China

    Dane Lin

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Lin, Z., Lin, D. & Lin, D. The Mechanisms of Adipose Stem Cell-Derived Exosomes Promote Wound Healing and Regeneration. Aesth Plast Surg (2024). https://doi.org/10.1007/s00266-024-03871-z

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