- College of Bioengineering, Chongqing University, Chongqing 400030, P.R.China;
Mesenchymal stem cells (MSCs) are pluripotent stem cells with high self-proliferation and multidirectional differentiation potential. They also have other functions including immune regulation, paracrine and so on, playing an important role in repairing injured tissues. In recent years, a lot of research has been done on how MSCs promote skin injury repair, and a lot of progress has been made. Compared with direct injection of MSCs in the wound area, some special treatments or transplantation methods could enhance the ability of MSCs to repair skin injury. This paper mainly discusses the role of MSCs in skin injury repair and technical ways to improve its repairing capacity, and discusses the existing problems in this field and prospects for future research directions.
Citation: CHENG Yansiwei, SONG Guanbin. Mesenchymal stem cells and skin injury repair. Journal of Biomedical Engineering, 2021, 38(2): 387-392. doi: 10.7507/1001-5515.202011017 Copy
1. | Sagaradze G D, Basalova N A, Efimenko A Y, et al. Mesenchymal stromal cells as critical contributors to tissue regeneration. Front Cell Dev Biol, 2020, 8: 576176. |
2. | Berebichez-Fridman R, Montero-Olvera P R. Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J, 2018, 18(3): e264-e277. |
3. | Gazdic M, Volarevic V, Arsenijevic N, et al. Mesenchymal stem cells: a friend or foe in immune-mediated diseases. Stem Cell Rev Rep, 2015, 11(2): 280-287. |
4. | Jiménez G, López de Andrés J, Marchal J A. Stem cell-secreted factors in the tumor microenvironment. Adv Exp Med Biol, 2020, 1277: 115-126. |
5. | Tsuchiya A, Takeuchi S, Watanabe T, et al. Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration. Inflamm Regen, 2019, 39: 18. |
6. | Praveen Kumar L, Kandoi S, Misra R, et al. The mesenchymal stem cell secretome: a new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev, 2019, 46: 1-9. |
7. | Pan H, Lam P K, Tong S W, et al. Mesenchymal stem cells combined with tissue fusion technology promoted wound healing in porcine bowel anastomosis. Stem Cells Int, 2020, 2020: 5142797. |
8. | Zhu M, Chu Y, Shang Q, et al. Mesenchymal stromal cells pretreated with pro-inflammatory cytokines promote skin wound healing through VEGFC-mediated angiogenesis. Stem Cells Transl Med, 2020, 9(10): 1218-1232. |
9. | Raghuram A C, Yu R P, Lo A Y, et al. Role of stem cell therapies in treating chronic wounds: a systematic review. World J Stem Cells, 2020, 12(7): 659-675. |
10. | Zahorec P, Sarkozyova N, Ferancikova N, et al. Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study. Cell Tissue Bank, 2021, 22(1): 39-46. |
11. | Athanerey A, Patra P K, Kumar A. Mesenchymal stem cell in venous leg ulcer: an intoxicating therapy. J Tissue Viabil, 2017, 26(3): 216-223. |
12. | Tsai H W, Wang P H, Tsui K H. Mesenchymal stem cell in wound healing and regeneration. J Chin Med Assoc, 2018, 81(3): 223-224. |
13. | Khademi B, Safari S, Mosleh-Shirazi M A, et al. Therapeutic effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats. Stem Cell Investig, 2020, 7: 12. |
14. | Sasaki M, Abe R, Fujita Y, et al. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol, 2008, 180(4): 2581-2587. |
15. | Wu Y, Chen L, Scott P G, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells, 2007, 25(10): 2648-2659. |
16. | Motegi S I, Ishikawa O. Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci, 2017, 86(2): 83-89. |
17. | Higashiyama R, Nakao S, Shibusawa Y, et al. Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice. J Invest Dermatol, 2011, 131(2): 529-536. |
18. | Day A J, Milner C M. TSG-6: a multifunctional protein with anti-inflammatory and tissue-protective properties. Matrix Biol, 2019, 78-79: 60-83. |
19. | Zhang S, Chen L, Zhang G, et al. Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages. Stem Cell Res Ther, 2020, 11(1): 39. |
20. | Riccobono D, Nikovics K, François S, et al. First insights into the M2 inflammatory response after adipose-tissue-derived stem cell injections in radiation-injured muscles. Health Phys, 2018, 115(1): 37-48. |
21. | Hofer H R, Tuan R S. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther, 2016, 7(1): 131. |
22. | Lee D E, Ayoub N, Agrawal D K. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther, 2016, 7: 37. |
23. | Loomans C J, de Koning E J, Staal F J, et al. Endothelial progenitor cell dysfunction: A novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes, 2004, 53(1): 195-199. |
24. | Zhao F Y, Cheng T Y, Yang L, et al. G-CSF inhibits pulmonary fibrosis by promoting bmsc homing to the lungs via SDF-1/CXCR4 chemotaxis. Sci Rep, 2020, 10(1): 10515. |
25. | Mohajer Ansari J, Ramhormozi P, Shabani R, et al. Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1α/CXCR4 pathway. Iran J Basic Med Sci, 2020, 23(6): 751-759. |
26. | Zhang B, Luo Q, Chen Z, et al. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells. Stem Cell Res, 2015, 14(2): 155-164. |
27. | Mao X, Chen Z, Luo Q, et al. Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness. Cytotechnology, 2016, 68(6): 2235-2243. |
28. | Lin C, Xu K, He Y, et al. A dynamic matrix potentiates mesenchymal stromal cell paracrine function via an effective mechanical dose. Biomater Sci, 2020, 8(17): 4779-4791. |
29. | Lozito T P, Tuan R S. Mesenchymal stem cells inhibit both endogenous and exogenous MMPs via secreted TIMPs. J Cell Physiol, 2011, 226(2): 385-396. |
30. | Ahangar P, Mills S J, Cowin A J. Mesenchymal stem cell secretome as an emerging cell-free alternative for improving wound repair. Int J Mol Sci, 2020, 21(19): 7038. |
31. | 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. |
32. | Li X, Xie X, Lian W, et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model. Exp Mol Med, 2018, 50(4): 1-14. |
33. | Pelizzo G, Avanzini M A, Icaro Cornaglia A, et al. Extracellular vesicles derived from mesenchymal cells: Perspective treatment for cutaneous wound healing in pediatrics. Regen Med, 2018, 13(4): 385-394. |
34. | Ferreira A D F, Cunha P D S, Carregal V M, et al. Extracellular vesicles from adipose-derived mesenchymal stem/stromal cells accelerate migration and activate AKT pathway in human keratinocytes and fibroblasts independently of miR-205 activity. Stem Cells Int, 2017, 2017: 9841035. |
35. | Liu J, Yan Z, Yang F, et al. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate cutaneous wound healing by enhancing angiogenesis through delivering angiopoietin-2. Stem Cell Rev Rep, 2020. DOI: 10.1007/s12015-020-09992-7. |
36. | Zhang B, Wang M, Gong A, et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem Cells, 2015, 33(7): 2158-2168. |
37. | Shojaei F, Rahmati S, Banitalebi Dehkordi M. A review on different methods to increase the efficiency of mesenchymal stem cell-based wound therapy. Wound Repair Regen, 2019, 27(6): 661-671. |
38. | Chen J S, Wong V W, Gurtner G C. Therapeutic potential of bone marrow-derived mesenchymal stem cells for cutaneous wound healing. Front Immunol, 2012, 3: 192. |
39. | Fromer M W, Chang S, Hagaman A L R, et al. The endothelial cell secretome as a novel treatment to prime adipose-derived stem cells for improved wound healing in diabetes. J Vasc Surg, 2018, 68(1): 234-244. |
40. | Arezoumand K S, Alizadeh E, Esmaeillou M, et al. The emu oil emulsified in egg lecithin and butylated hydroxytoluene enhanced the proliferation, stemness gene expression, and in vitro wound healing of adipose-derived stem cells. In Vitro Cell Dev Biol Anim, 2018, 54(3): 205-216. |
41. | Zhang Y, Niu X, Dong X, et al. Bioglass enhanced wound healing ability of urine-derived stem cells through promoting paracrine effects between stem cells and recipient cells. J Tissue Eng Regen Med, 2018, 12(3): e1609-e1622. |
42. | Yang Z, He C, He J, et al. Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing. Stem Cell Res Ther, 2018, 9(1): 21. |
43. | 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. |
44. | Gao M, Zhang J, Wang J Z, et al. Effects of hypoxia-pretreated rat adipose-derived mesenchymal stem cells conditioned medium on wound healing of rats with full-thickness defects. Zhonghua Shao Shang Za Zhi, 2020, 36(9): 803-812. |
45. | Li M, Qiu L, Hu W, et al. Genetically-modified bone mesenchymal stem cells with TGF-β(3) improve wound healing and reduce scar tissue formation in a rabbit model. Exp Cell Res, 2018, 367(1): 24-29. |
46. | Xiao S, Huang G, Wei Z, et al. IL-10 gene-modified human amniotic mesenchymal stem cells augment regenerative wound healing by multiple synergistic effects. Stem Cells Int, 2019, 2019: 9158016. |
47. | Bai H, Kyu-Cheol N, Wang Z, et al. Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers. J Tissue Eng, 2020, 11: 2041731420947242. |
48. | Dash B C, Xu Z, Lin L, et al. Stem cells and engineered scaffolds for regenerative wound healing. Bioengineering (Basel), 2018, 5(1): 23. |
49. | Yao M, Zhang J, Gao F, et al. New BMSC-laden gelatin hydrogel formed in situ by dual-enzymatic cross-linking accelerates dermal wound healing. ACS omega, 2019, 4(5): 8334-8340. |
50. | Kaisang L, Siyu W, Lijun F, et al. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing. J Surg Res, 2017, 217: 63-74. |
51. | Lei Z, Singh G, Min Z, et al. Bone marrow-derived mesenchymal stem cells laden novel hermos-sensitive hydrogel for the management of severe skin wound healing. Mater Sci Eng C Mater Biol Appl, 2018, 90: 159-167. |
52. | Stessuk T, Puzzi M B, Chaim E A, et al. Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro. Arch Dermatol Res, 2016, 308(7): 511-520. |
53. | Mahmoudian-Sani M R, Rafeei F, Amini R, et al. The effect of mesenchymal stem cells combined with platelet-rich plasma on skin wound healing. J Cosmet Dermatol, 2018, 17(5): 650-659. |
54. | Chu J, Shi P, Deng X, et al. Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing. J Biophotonics, 2018, 11(7): e201700336. |
55. | Qi Y, Dong Z, Chu H, et al. Denatured acellular dermal matrix seeded with bone marrow mesenchymal stem cells for wound healing in mice. Burns, 2019, 45(7): 1685-1694. |
56. | Murphy K C, Whitehead J, Zhou D, et al. Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. Acta Biomater, 2017, 64: 176-186. |
57. | Huang S, Wu Y, Gao D, et al. Paracrine action of mesenchymal stromal cells delivered by microspheres contributes to cutaneous wound healing and prevents scar formation in mice. Cytotherapy, 2015, 17(7): 922-931. |
58. | Yu J, Wang M Y, Tai H C, et al. Cell sheet composed of adipose-derived stem cells demonstrates enhanced skin wound healing with reduced scar formation. Acta Biomater, 2018, 77: 191-200. |
59. | Koo M A, Hee Hong S, Hee Lee M, et al. Effective stacking and transplantation of stem cell sheets using exogenous ROS-producing film for accelerated wound healing. Acta Biomater, 2019, 95: 418-426. |
- 1. Sagaradze G D, Basalova N A, Efimenko A Y, et al. Mesenchymal stromal cells as critical contributors to tissue regeneration. Front Cell Dev Biol, 2020, 8: 576176.
- 2. Berebichez-Fridman R, Montero-Olvera P R. Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J, 2018, 18(3): e264-e277.
- 3. Gazdic M, Volarevic V, Arsenijevic N, et al. Mesenchymal stem cells: a friend or foe in immune-mediated diseases. Stem Cell Rev Rep, 2015, 11(2): 280-287.
- 4. Jiménez G, López de Andrés J, Marchal J A. Stem cell-secreted factors in the tumor microenvironment. Adv Exp Med Biol, 2020, 1277: 115-126.
- 5. Tsuchiya A, Takeuchi S, Watanabe T, et al. Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration. Inflamm Regen, 2019, 39: 18.
- 6. Praveen Kumar L, Kandoi S, Misra R, et al. The mesenchymal stem cell secretome: a new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev, 2019, 46: 1-9.
- 7. Pan H, Lam P K, Tong S W, et al. Mesenchymal stem cells combined with tissue fusion technology promoted wound healing in porcine bowel anastomosis. Stem Cells Int, 2020, 2020: 5142797.
- 8. Zhu M, Chu Y, Shang Q, et al. Mesenchymal stromal cells pretreated with pro-inflammatory cytokines promote skin wound healing through VEGFC-mediated angiogenesis. Stem Cells Transl Med, 2020, 9(10): 1218-1232.
- 9. Raghuram A C, Yu R P, Lo A Y, et al. Role of stem cell therapies in treating chronic wounds: a systematic review. World J Stem Cells, 2020, 12(7): 659-675.
- 10. Zahorec P, Sarkozyova N, Ferancikova N, et al. Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study. Cell Tissue Bank, 2021, 22(1): 39-46.
- 11. Athanerey A, Patra P K, Kumar A. Mesenchymal stem cell in venous leg ulcer: an intoxicating therapy. J Tissue Viabil, 2017, 26(3): 216-223.
- 12. Tsai H W, Wang P H, Tsui K H. Mesenchymal stem cell in wound healing and regeneration. J Chin Med Assoc, 2018, 81(3): 223-224.
- 13. Khademi B, Safari S, Mosleh-Shirazi M A, et al. Therapeutic effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats. Stem Cell Investig, 2020, 7: 12.
- 14. Sasaki M, Abe R, Fujita Y, et al. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol, 2008, 180(4): 2581-2587.
- 15. Wu Y, Chen L, Scott P G, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells, 2007, 25(10): 2648-2659.
- 16. Motegi S I, Ishikawa O. Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci, 2017, 86(2): 83-89.
- 17. Higashiyama R, Nakao S, Shibusawa Y, et al. Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice. J Invest Dermatol, 2011, 131(2): 529-536.
- 18. Day A J, Milner C M. TSG-6: a multifunctional protein with anti-inflammatory and tissue-protective properties. Matrix Biol, 2019, 78-79: 60-83.
- 19. Zhang S, Chen L, Zhang G, et al. Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages. Stem Cell Res Ther, 2020, 11(1): 39.
- 20. Riccobono D, Nikovics K, François S, et al. First insights into the M2 inflammatory response after adipose-tissue-derived stem cell injections in radiation-injured muscles. Health Phys, 2018, 115(1): 37-48.
- 21. Hofer H R, Tuan R S. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther, 2016, 7(1): 131.
- 22. Lee D E, Ayoub N, Agrawal D K. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther, 2016, 7: 37.
- 23. Loomans C J, de Koning E J, Staal F J, et al. Endothelial progenitor cell dysfunction: A novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes, 2004, 53(1): 195-199.
- 24. Zhao F Y, Cheng T Y, Yang L, et al. G-CSF inhibits pulmonary fibrosis by promoting bmsc homing to the lungs via SDF-1/CXCR4 chemotaxis. Sci Rep, 2020, 10(1): 10515.
- 25. Mohajer Ansari J, Ramhormozi P, Shabani R, et al. Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1α/CXCR4 pathway. Iran J Basic Med Sci, 2020, 23(6): 751-759.
- 26. Zhang B, Luo Q, Chen Z, et al. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells. Stem Cell Res, 2015, 14(2): 155-164.
- 27. Mao X, Chen Z, Luo Q, et al. Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness. Cytotechnology, 2016, 68(6): 2235-2243.
- 28. Lin C, Xu K, He Y, et al. A dynamic matrix potentiates mesenchymal stromal cell paracrine function via an effective mechanical dose. Biomater Sci, 2020, 8(17): 4779-4791.
- 29. Lozito T P, Tuan R S. Mesenchymal stem cells inhibit both endogenous and exogenous MMPs via secreted TIMPs. J Cell Physiol, 2011, 226(2): 385-396.
- 30. Ahangar P, Mills S J, Cowin A J. Mesenchymal stem cell secretome as an emerging cell-free alternative for improving wound repair. Int J Mol Sci, 2020, 21(19): 7038.
- 31. 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.
- 32. Li X, Xie X, Lian W, et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model. Exp Mol Med, 2018, 50(4): 1-14.
- 33. Pelizzo G, Avanzini M A, Icaro Cornaglia A, et al. Extracellular vesicles derived from mesenchymal cells: Perspective treatment for cutaneous wound healing in pediatrics. Regen Med, 2018, 13(4): 385-394.
- 34. Ferreira A D F, Cunha P D S, Carregal V M, et al. Extracellular vesicles from adipose-derived mesenchymal stem/stromal cells accelerate migration and activate AKT pathway in human keratinocytes and fibroblasts independently of miR-205 activity. Stem Cells Int, 2017, 2017: 9841035.
- 35. Liu J, Yan Z, Yang F, et al. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate cutaneous wound healing by enhancing angiogenesis through delivering angiopoietin-2. Stem Cell Rev Rep, 2020. DOI: 10.1007/s12015-020-09992-7.
- 36. Zhang B, Wang M, Gong A, et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem Cells, 2015, 33(7): 2158-2168.
- 37. Shojaei F, Rahmati S, Banitalebi Dehkordi M. A review on different methods to increase the efficiency of mesenchymal stem cell-based wound therapy. Wound Repair Regen, 2019, 27(6): 661-671.
- 38. Chen J S, Wong V W, Gurtner G C. Therapeutic potential of bone marrow-derived mesenchymal stem cells for cutaneous wound healing. Front Immunol, 2012, 3: 192.
- 39. Fromer M W, Chang S, Hagaman A L R, et al. The endothelial cell secretome as a novel treatment to prime adipose-derived stem cells for improved wound healing in diabetes. J Vasc Surg, 2018, 68(1): 234-244.
- 40. Arezoumand K S, Alizadeh E, Esmaeillou M, et al. The emu oil emulsified in egg lecithin and butylated hydroxytoluene enhanced the proliferation, stemness gene expression, and in vitro wound healing of adipose-derived stem cells. In Vitro Cell Dev Biol Anim, 2018, 54(3): 205-216.
- 41. Zhang Y, Niu X, Dong X, et al. Bioglass enhanced wound healing ability of urine-derived stem cells through promoting paracrine effects between stem cells and recipient cells. J Tissue Eng Regen Med, 2018, 12(3): e1609-e1622.
- 42. Yang Z, He C, He J, et al. Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing. Stem Cell Res Ther, 2018, 9(1): 21.
- 43. 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.
- 44. Gao M, Zhang J, Wang J Z, et al. Effects of hypoxia-pretreated rat adipose-derived mesenchymal stem cells conditioned medium on wound healing of rats with full-thickness defects. Zhonghua Shao Shang Za Zhi, 2020, 36(9): 803-812.
- 45. Li M, Qiu L, Hu W, et al. Genetically-modified bone mesenchymal stem cells with TGF-β(3) improve wound healing and reduce scar tissue formation in a rabbit model. Exp Cell Res, 2018, 367(1): 24-29.
- 46. Xiao S, Huang G, Wei Z, et al. IL-10 gene-modified human amniotic mesenchymal stem cells augment regenerative wound healing by multiple synergistic effects. Stem Cells Int, 2019, 2019: 9158016.
- 47. Bai H, Kyu-Cheol N, Wang Z, et al. Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers. J Tissue Eng, 2020, 11: 2041731420947242.
- 48. Dash B C, Xu Z, Lin L, et al. Stem cells and engineered scaffolds for regenerative wound healing. Bioengineering (Basel), 2018, 5(1): 23.
- 49. Yao M, Zhang J, Gao F, et al. New BMSC-laden gelatin hydrogel formed in situ by dual-enzymatic cross-linking accelerates dermal wound healing. ACS omega, 2019, 4(5): 8334-8340.
- 50. Kaisang L, Siyu W, Lijun F, et al. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing. J Surg Res, 2017, 217: 63-74.
- 51. Lei Z, Singh G, Min Z, et al. Bone marrow-derived mesenchymal stem cells laden novel hermos-sensitive hydrogel for the management of severe skin wound healing. Mater Sci Eng C Mater Biol Appl, 2018, 90: 159-167.
- 52. Stessuk T, Puzzi M B, Chaim E A, et al. Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro. Arch Dermatol Res, 2016, 308(7): 511-520.
- 53. Mahmoudian-Sani M R, Rafeei F, Amini R, et al. The effect of mesenchymal stem cells combined with platelet-rich plasma on skin wound healing. J Cosmet Dermatol, 2018, 17(5): 650-659.
- 54. Chu J, Shi P, Deng X, et al. Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing. J Biophotonics, 2018, 11(7): e201700336.
- 55. Qi Y, Dong Z, Chu H, et al. Denatured acellular dermal matrix seeded with bone marrow mesenchymal stem cells for wound healing in mice. Burns, 2019, 45(7): 1685-1694.
- 56. Murphy K C, Whitehead J, Zhou D, et al. Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. Acta Biomater, 2017, 64: 176-186.
- 57. Huang S, Wu Y, Gao D, et al. Paracrine action of mesenchymal stromal cells delivered by microspheres contributes to cutaneous wound healing and prevents scar formation in mice. Cytotherapy, 2015, 17(7): 922-931.
- 58. Yu J, Wang M Y, Tai H C, et al. Cell sheet composed of adipose-derived stem cells demonstrates enhanced skin wound healing with reduced scar formation. Acta Biomater, 2018, 77: 191-200.
- 59. Koo M A, Hee Hong S, Hee Lee M, et al. Effective stacking and transplantation of stem cell sheets using exogenous ROS-producing film for accelerated wound healing. Acta Biomater, 2019, 95: 418-426.