Mesenchymal stem cells in skin wound healing

Year 2016, Volume: 10 Issue: 3, 228 - 234, 30.12.2016

Işıl Aydemir Şamil Öztürk Pınar Kılıçaslan Sönmez , Mehmet İbrahim Tuğlu

Abstract

The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. Chronic conditions such as diabetes mellitus or peripheral vascular diseases can lead to impaired wound healing. Skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. This is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications. Mesenchymal stem cells have an alternative role due to special properties such as the capacity for self-renewal and multi-lineage differentiation, immunomodulatory effect, alleviation of inflammatory response, induction of angiogenesis, regulation of extracellular matrix remodeling, excellent migration and secretion of growth factors and cytokines in wound healing. We summarized current research on the mechanisms of mesenchymal stem cells with their isolation, specific markers, differentiation capacity, and the functional activities to evaluate wound healing application.

Keywords

mesenchymal stem cell, skin, wound healing

References

• 1. Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 2016;58:81–94.
• 2. PikuΠa M, Langa P, Kosikowska P, Trzonkowski P. Stem cells and growth factors in wound healing. Postepy Hig Med Dosw 2015; 69:874–85.
• 3. Tuca AC, Ertl J, Hingerl K, Pichlsberger M, Fuchs J, Wurzer P, Pfeiffer D, Bubalo V, Parvizi D, Kamolz LP, Lang I. Comparison of Matrigel and atriderm as a carrier for human amnion-derived mesenchymal stem cells in wound healing. Placenta 2016;48:99–103.
• 4. Motegi SI, Ishikawa O. Mesenchymal stem cells: the roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci Epub 2016 DOI 10.1016/j.jdermsci.2016.11.005.
• 5. Yao Z, Li H, He W, Yang S, Zhang X, Zhan R, Xu R, Tan J, Zhou J, Wu J, Luo G. P311 accelerates skin wound reepithelialization by promoting epidermal stem cell migration through Rho A and Rac1 activation. Stem Cells Dev Epub 2016 Dec 8.
• 6. Tao SC, Guo SC, Li M, Ke QF, Guo YP, Zhang CQ. Chitosan wound dressings incorporating exosomes derived from microrna- 126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl Med Epub 2016 DOI 10.5966/sctm.2016–0275
• 7. Surrao DC, Boon K, Borys B, Sinha S, Kumar R, Biernaskie J, Kallos MS. Large-scale expansion of human skin-derived precursor cells (hSKPs) in stirred suspension bioreactors. Biotechnol Bioeng 2016;113:2725–38.
• 8. Shi R, Jin Y, Cao C, Han S, Shao X, Meng L, Cheng J, Zhang M, Zheng J, Xu J, Li M. Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats. Stem Cell Res Ther 2016;7:155.
• 9. Rajabian MH, Ghorabi GH, Geramizadeh B, Sameni S, Ayatollahi M. Evaluation of bone marrow derived mesenchymal stem cells for full-thickness wound healing in comparison to tissue engineered chitosan scaffold in rabbit. Tissue Cell 2016 Epub DOI 10.1016/j.tice. 2016.11.002.
• 10. Prockop DJ. Repair of tissues by adult stem/progenitor cells (MSCs):controversies, myths, and changing paradigms. Mol Ther 2009;17:939–46.
• 11. Lee DE, Ayoub N, Agrawal DK. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther 2016;7:37.
• 12. Li H, Ghazanfari R, Zacharaki D, Lim HC, Scheding S. Isolation and characterization of primary bone marrow mesenchymal stromal cells. Ann N Y Acad Sci 2016;1370:109–18.
• 13. Owen M, Friedenstein AJ. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 1988;136:42–60.
• 14. Cakiroglu F, Osbahr JW, Kramer J, Rohwedel J. Differences of cell surface marker expression between bone marrow- and kidneyderived murine mesenchymal stromal cells and fibroblasts. Cell Mol Biol (Noisy-le-grand) 2016;62:11–7.
• 15. Battula VL, Treml S, Bareiss PM, Gieseke F, Roelofs H, de Zwart P, Müller I, Schewe B, Skutella T, Fibbe WE, Kanz L, Bühring HJ. Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen- 1. Haematologica 2009;94:173–84.
• 16. Matic I, Antunovic M, Brkic S, Josipovic P, Mihalic KC, Karlak I, Ivkovic A, Marijanovic I. Expression of OCT-4 and SOX-2 in Bone marrow-derived human mesenchymal stem cells during osteogenic differentiation. Open Access Maced J Med Sci 2016;4:9–16.
• 17. Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell 2015;16:239–53.
• 18. Maleki M, Ghanbarvand F, Reza Behvarz M, Ejtemaei M, Ghadirkhomi E. Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells 2014;7:118–26.
• 19. Mohammadi Z, Afshari JT, Keramati MR, Alamdari DH, Ganjibakhsh M, Zarmehri AM, Jangjoo A, Sadeghian MH, Ameri MA, Moinzadeh L. Differentiation of adipocytes and osteocytes from human adipose and placental mesenchymal stem cells. Iran J Basic Med Sci 2015;18:259-66.
• 20. Baustian C, Hanley S, Ceredig R. Isolation, selection and culture methods to enhance clonogenicity of mouse bone marrow derived mesenchymal stromal cell precursors. Stem Cell Res Ther 2015;6: 151.
• 21. Walmsley GG, Atashroo DA, Maan ZN, Hu MS, Zielins ER, Tsai JM, Duscher D, Paik K, Tevlin R, Marecic O, Wan DC, Gurtner GC, Longaker MT. High-throughput screening of surface marker expression on undifferentiated and differentiated human adiposederived stromal cells. Tissue Eng Part A 2015;21:2281–91.
• 22. Liu Y, Strecker S, Wang L, Kronenberg MS, Wang W, Rowe DW, Maye P. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma. PLoS One 2013; 8:e71318.
• 23. Lin SS, Ueng SW, Niu CC, Yuan LJ, Yang CY, Chen WJ, Lee MS, Chen JK. Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells. BMC Musculoskelet Disord 2014; 15:56.
• 24. Zhang LY, Xue HG, Chen JY, Chai W, Ni M. Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARÁ. Exp Ther Med 2016;11:1853–8.
• 25. Menicanin D, Bartold PM, Zannettino AC, Gronthos S. Genomic profiling of mesenchymal stem cells. Stem Cell Rev 2009;5:36–50.
• 26. Xu J, Li Z, Hou Y, Fang W. Potential mechanisms underlying the Runx2 induced osteogenesis of bone marrow mesenchymal stem cells. Am J Transl Res 2015;7:2527–35.
• 27. Amos PJ, Mulvey CL, Seaman SA, Walpole J, Degen KE, Shang H, Katz AJ, Peirce SM. Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells. Am J Physiol Cell Physiol 2011;301:C1378–88.
• 28. Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene 2009;433:1–7.
• 29. Portou MJ, Baker D, Abraham D, Tsui J. The innate immune system, toll-like receptors and dermal wound healing: a review. Vascul Pharmacol 2015;71:31–6.
• 30. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle) 2015;4:560–82.
• 31. Hocking AM. Mesenchymal stem cell therapy for cutaneous wounds. Adv Wound Care (New Rochelle) 2012;1:166–71.
• 32. Li M, Xu J, Shi T, Yu H, Bi J, Chen G. Epigallocatechin-3-gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing. Clin Exp Pharmacol Physiol 2016;43:1115–24.
• 33. Tamama K, Kerpedjieva SS. Acceleration of wound healing by multiple growth factors and cytokines secreted from multipotential stromal cells/mesenchymal stem cells. Adv Wound Care (New Rochelle) 2012;1:177–82.
• 34. Lafosse A, Dufeys C, Beauloye C, Horman S, Dufrane D. Impact of hyperglycemia and low oxygen tension on adipose-derived stem cells compared with dermal fibroblasts and keratinocytes: importance for wound healing in type 2 diabetes. PLoS One 2016;11:e0168058.
• 35. Maxson S, Lopez EA, Yoo D, Miagkova AD, LeRoux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med 2012;1:142–9.
• 36. Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci 2015;16:25476–501.
• 37. Tao H, Han Z, Han ZC, Li Z. Proangiogenic features of mesenchymal stem cells and their therapeutic applications. Stem Cells Int 2016;2016:1314709.
• 38. Ghieh F, Jurjus R, Ibrahim A, Geagea AG, Daouk H, Baba BE, Chams S, Matar M, Zein W, Jurjus A The use of stem cells in burn wound healing: a review. Biomed Res Int 2015;2015:684084.
• 39. Midwood KS, Williams LV, Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 2004;36:1031–7.
• 40. Ballas CB, Davidson JM. Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2001;9:223–37.
• 41. Kim BC, Kim HT, Park SH, et al. Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta Type II receptor expression. J Cell Physiol 2003;195:331–6.
• 42. Zaulyanov L, Kirsner RS. A review of a bi-layered living cell treatment (Apligraf®) in the treatment of venous leg ulcers and diabetic foot ulcers. Clin Interv Aging 2007;2:93–8.
• 43. Agren MS, Steenfos HH, Dabelsteen S, et al. Proliferation and mitogenic response to PDGF-BB of fibroblasts isolated from chronic venous leg ulcers is ulcer-age dependent. J Invest Dermatol 1999; 112:463–9.
• 44. Wankhade UD, Shen M, Kolhe R, Fulzele S. Advances in adiposederived stem cells isolation, characterization, and application in regenerative tissue engineering. Stem Cells Int 2016;2016:3206807.