Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

M Isakson, C de Blacam, D Whelan, A McArdle, A J P Clover, M Isakson, C de Blacam, D Whelan, A McArdle, A J P Clover

Abstract

Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

Figures

Figure 1
Figure 1
Multilineage potential of MSCs (mesenchymal stem cells), such as bone-marrow-derived mesenchymal stromal cells and adipose-derived stromal cells, has the potential to differentiate into various lineages, making them ideal candidates for cell-based tissue engineering strategies. It has been demonstrated that MSCs can undergo osteogenesis, chondrogenesis, adipogenesis, and myogenesis.
Figure 2
Figure 2
Prisma flowchart for systematic review. Flowchart demonstrating the selection criteria for research papers included in this review. Overall 56 papers were evaluated in this systematic review, including 50 using animal models and 6 using human trials.
Figure 3
Figure 3
Studies in cutaneous wound healing were performed in a diverse range of animal models. Animal models used for cutaneous wound healing studies are not standardized. (a) Most studies of cutaneous wound healing were performed using excisional wound models in 65% of studies. Other models included incisional wounds and burn models. (b) Most studies were carried out in mouse models (55% of studies) with other models including rat, human, pig, and rabbit models.
Figure 4
Figure 4
MSCs and ASCs act to promote cutaneous wound healing through a variety of mechanisms. MSCs and ASCs influence wound healing through a variety of mechanisms, including angiogenesis, promoting epithelialization, and enhancing collagen deposition and granulation tissue formation. In addition, various studies have demonstrated that transplanted cells engraft into the wound to participate in wound healing. Blue bars represent studies examining BM-MSCs and orange bars represent studies evaluating ASCs.
Figure 5
Figure 5
Work flow of cell-based regenerative therapy. An ideal regenerative medicine strategy requires three components: an ideal cell type, biomimetic scaffold, and factors to create the desired biological response in vivo. Cutaneous wounds represent a harsh environment for cellular therapy due to their hypoxic environment and low pH which can affect the survival and potential of transplanted cells. The niche microenvironment can be manipulated with the use of scaffolds and growth factors to enhance cellular survival, promote cellular differentiation, and ultimately enhance wound healing in the clinical setting. Reproduced with permission from the authors: McArdle, Paik, Chung, Hu, and Walmsley et al. (2013) Manipulation of Stem Cells and their Microenvironment for Tissue Engineering. Surgery Curr Res 3 : 134.

References

    1. Maan Z. N., Januszyk M., Rennert R. C., et al. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plastic and Reconstructive Surgery. 2014;134(3):402e–411e. doi: 10.1097/prs.0000000000000467.
    1. Posnett J., Gottrup F., Lundgren H., Saal G. The resource impact of wounds on health-care providers in Europe. Journal of Wound Care. 2009;18(4):154–161. doi: 10.12968/jowc.2009.18.4.41607.
    1. Hu M. S., Maan Z. N., Wu J. C., et al. Tissue engineering and regenerative repair in wound healing. Annals of Biomedical Engineering. 2014;42(7):1494–1507.
    1. Singer A. J., Clark R. A. F. Cutaneous wound healing. The New England Journal of Medicine. 1999;341(10):738–746. doi: 10.1056/nejm199909023411006.
    1. Ilan N., Mahooti S., Madri J. A. Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis. Journal of Cell Science. 1998;111, part 24:3621–3631.
    1. McInnes E., Bell-Syer S. E., Dumville J. C., Legood R., Cullum N. A. Support surfaces for pressure ulcer prevention. Cochrane Database of Systematic Reviews. 2008;(4)CD001735
    1. O'Meara S., Cullum N., Nelson E. A., Dumville J. C. Compression for venous leg ulcers. Cochrane Database of Systematic Reviews. 2012;11 doi: 10.1002/14651858.CD000265.pub3.CD000265
    1. Pittenger M. F., Mackay A. M., Beck S. C., et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147. doi: 10.1126/science.284.5411.143.
    1. McArdle A., Chung M. T., Paik K. J., et al. Positive selection for bone morphogenetic protein receptor type-IB promotes differentiation and specification of human adipose-derived stromal cells toward an osteogenic lineage. Tissue Engineering Part A. 2014;20(21-22):3031–3040. doi: 10.1089/ten.tea.2014.0101.
    1. Zuk P. A., Zhu M., Ashjian P., et al. Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell. 2002;13(12):4279–4295. doi: 10.1091/mbc.E02-02-0105.
    1. Zuk P. A., Zhu M., Mizuno H., et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Engineering. 2001;7(2):211–228. doi: 10.1089/107632701300062859.
    1. Cowan C. M., Shi Y.-Y., Aalami O. O., et al. Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nature Biotechnology. 2004;22(5):560–567. doi: 10.1038/nbt958.
    1. Zuk P. A. Tissue engineering craniofacial defects with adult stem cells? Are we ready yet? Pediatric Research. 2008;63(5):478–486. doi: 10.1203/PDR.0b013e31816bdf36.
    1. Gimble J. M., Katz A. J., Bunnell B. A. Adipose-derived stem cells for regenerative medicine. Circulation Research. 2007;100(9):1249–1260. doi: 10.1161/01.res.0000265074.83288.09.
    1. Altman A. M., Matthias N., Yan Y., et al. Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells. Biomaterials. 2008;29(10):1431–1442. doi: 10.1016/j.biomaterials.2007.11.026.
    1. Altman A. M., Yan Y., Matthias N., et al. IFATS collection: human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model. Stem Cells. 2009;27(1):250–258. doi: 10.1634/stemcells.2008-0178.
    1. Argôlo Neto N. M., Del Carlo R. J., Monteiro B. S., et al. Role of autologous mesenchymal stem cells associated with platelet-rich plasma on healing of cutaneous wounds in diabetic mice. Clinical and Experimental Dermatology. 2012;37(5):544–553. doi: 10.1111/j.1365-2230.2011.04304.x.
    1. Blanton M. W., Hadad I., Johnstone B. H., et al. Adipose stromal cells and platelet-rich plasma therapies synergistically increase revascularization during wound healing. Plastic and Reconstructive Surgery. 2009;123(2):56S–64S. doi: 10.1097/prs.0b013e318191be2d.
    1. Borena B. M., Pawde A. M., Aithal H. P., Kinjavdekar P., Singh R., Kumar D. Evaluation of autologous bone marrow-derived nucleated cells for healing of full-thickness skin wounds in rabbits. International Wound Journal. 2010;7(4):249–260. doi: 10.1111/j.1742-481x.2010.00683.x.
    1. Chen L., Tredget E. E., Liu C., Wu Y. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS ONE. 2009;4(9) doi: 10.1371/journal.pone.0007119.e7119
    1. Chen L., Tredget E. E., Wu P. Y. G., Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS ONE. 2008;3(4) doi: 10.1371/journal.pone.0001886.e1886
    1. Cho J.-W., Kang M.-C., Lee K.-S. TGF-β1-treated ADSCs-CM promotes expression of type I collagen and MMP-1, migration of human skin fibroblasts, and wound healing in vitro and in vivo. International Journal of Molecular Medicine. 2010;26(6):901–906. doi: 10.3892/ijmm-00000540.
    1. Ebrahimian T. G., Pouzoulet F., Squiban C., et al. Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29(4):503–510. doi: 10.1161/atvbaha.108.178962.
    1. Falanga V., Iwamoto S., Chartier M., et al. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Engineering. 2007;13(6):1299–1312. doi: 10.1089/ten.2006.0278.
    1. Fu X., Fang L., Li H., Li X., Cheng B., Sheng Z. Adipose tissue extract enhances skin wound healing. Wound Repair and Regeneration. 2007;15(4):540–548. doi: 10.1111/j.1524-475X.2007.00262.x.
    1. Fu X., Fang L., Li X., Cheng B., Sheng Z. Enhanced wound-healing quality with bone marrow mesenchymal stem cells autografting after skin injury. Wound Repair and Regeneration. 2006;14(3):325–335. doi: 10.1111/j.1743-6109.2006.00128.x.
    1. Gao W., Qiao X., Ma S., Cui L. Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α . Journal of Cellular and Molecular Medicine. 2011;15(12):2575–2585. doi: 10.1111/j.1582-4934.2011.01313.x.
    1. Gu J. H., Lee J. S., Kim D.-W., Yoon E.-S., Dhong E.-S. Neovascular potential of adipose-derived stromal cells (ASCs) from diabetic patients. Wound Repair and Regeneration. 2012;20(2):243–252. doi: 10.1111/j.1524-475X.2012.00765.x.
    1. Hamou C., Callaghan M. J., Thangarajah H., et al. Mesenchymal stem cells can participate in ischemic neovascularization. Plastic and Reconstructive Surgery. 2009;123(2, supplement):45S–55S. doi: 10.1097/PRS.0b013e318191be4a.
    1. Heo S. C., Jeon E. S., Lee I. H., Kim H. S., Kim M. B., Kim J. H. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. Journal of Investigative Dermatology. 2011;131(7):1559–1567. doi: 10.1038/jid.2011.64.
    1. Hou C., Shen L., Huang Q., et al. The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer. Biomaterials. 2013;34(1):112–120. doi: 10.1016/j.biomaterials.2012.09.022.
    1. Huang S., Lu G., Wu Y., et al. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair. Journal of Dermatological Science. 2012;66(1):29–36. doi: 10.1016/j.jdermsci.2012.02.002.
    1. Javazon E. H., Keswani S. G., Badillo A. T., et al. Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic mice treated with adult murine bone marrow stromal progenitor cells. Wound Repair and Regeneration. 2007;15(3):350–359. doi: 10.1111/j.1524-475X.2007.00237.x.
    1. Kataoka K., Medina R. J., Kageyama T., et al. Participation of adult mouse bone marrow cells in reconstitution of skin. American Journal of Pathology. 2003;163(4):1227–1231. doi: 10.1016/s0002-9440(10)63482-7.
    1. Kim C. H., Lee J. H., Won J. H., Cho M. K. Mesenchymal stem cells improve wound healing in vivo via early activation of matrix metalloproteinase-9 and vascular endothelial growth factor. Journal of Korean Medical Science. 2011;26(6):726–733. doi: 10.3346/jkms.2011.26.6.726.
    1. Kim W.-S., Park B.-S., Sung J.-H., et al. Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. Journal of Dermatological Science. 2007;48(1):15–24. doi: 10.1016/j.jdermsci.2007.05.018.
    1. Kim H., Choi K., Kweon O.-K., Kim W. H. Enhanced wound healing effect of canine adipose-derived mesenchymal stem cells with low-level laser therapy in athymic mice. Journal of Dermatological Science. 2012;68(3):149–156. doi: 10.1016/j.jdermsci.2012.09.013.
    1. Kwon D. S., Gao X., Liu Y. B., et al. Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. International Wound Journal. 2008;5(3):453–463. doi: 10.1111/j.1742-481x.2007.00408.x.
    1. Lee S., Szilagyi E., Chen L., et al. Activated mesenchymal stem cells increase wound tensile strength in aged mouse model via macrophages. Journal of Surgical Research. 2013;181(1):20–24. doi: 10.1016/j.jss.2012.05.040.
    1. Lee E. Y., Xia Y., Kim W.-S., et al. Hypoxia-enhanced wound-healing function of adipose-derived stem cells: Increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair and Regeneration. 2009;17(4):540–547. doi: 10.1111/j.1524-475X.2009.00499.x.
    1. Lee S. H., Lee J. H., Cho K. H. Effects of human adipose-derived stem cells on cutaneous wound healing in nude mice. Annals of Dermatology. 2011;23(2):150–155. doi: 10.5021/ad.2011.23.2.150.
    1. Li H., Fu X., Ouyang Y., Cai C., Wang J., Sun T. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell and Tissue Research. 2006;326(3):725–736. doi: 10.1007/s00441-006-0270-9.
    1. Lim J. S., Yoo G. Effects of adipose-derived stromal cells and of their extract on wound healing in a mouse model. Journal of Korean Medical Science. 2010;25(5):746–751. doi: 10.3346/jkms.2010.25.5.746.
    1. Lin Y.-C., Grahovac T., Oh S. J., Ieraci M., Rubin J. P., Marra K. G. Evaluation of a multi-layer adipose-derived stem cell sheet in a full-thickness wound healing model. Acta Biomaterialia. 2013;9(2):5243–5250. doi: 10.1016/j.actbio.2012.09.028.
    1. Liu P., Deng Z., Han S., et al. Tissue-engineered skin containing mesenchymal stem cells improves burn wounds. Artificial Organs. 2008;32(12):925–931. doi: 10.1111/j.1525-1594.2008.00654.x.
    1. Liu S., Zhang H., Zhang X., et al. Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. Tissue Engineering: Part A. 2011;17(5-6):725–739. doi: 10.1089/ten.tea.2010.0331.
    1. Maharlooei M. K., Bagheri M., Solhjou Z., et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice. 2011;93(2):228–234. doi: 10.1016/j.diabres.2011.04.018.
    1. Mansilla E., Spretz R., Larsen G., et al. Outstanding survival and regeneration process by the use of intelligent acellular dermal matrices and mesenchymal stem cells in a burn pig model. Transplantation Proceedings. 2010;42(10):4275–4278. doi: 10.1016/j.transproceed.2010.09.132.
    1. McFarlin K., Gao X., Liu Y. B., et al. Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat. Wound Repair and Regeneration. 2006;14(4):471–478. doi: 10.1111/j.1743-6109.2006.00153.x.
    1. Nakagawa H., Akita S., Fukui M., Fujii T., Akino K. Human mesenchymal stem cells successfully improve skin-substitute wound healing. British Journal of Dermatology. 2005;153(1):29–36. doi: 10.1111/j.1365-2133.2005.06554.x.
    1. Nambu M., Kishimoto S., Nakamura S., et al. Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix. Annals of Plastic Surgery. 2009;62(3):317–321. doi: 10.1097/sap.0b013e31817f01b6.
    1. Nambu M., Ishihara M., Nakamura S., et al. Enhanced healing of mitomycin C-treated wounds in rats using inbred adipose tissue-derived stromal cells within an atelocollagen matrix. Wound Repair and Regeneration. 2007;15(4):505–510. doi: 10.1111/j.1524-475X.2007.00258.x.
    1. Nie C., Yang D., Xu J., Si Z., Jin X., Zhang J. Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplantation. 2011;20(2):205–216. doi: 10.3727/096368910x520065.
    1. Rasulov M. F., Vasilenko V. T., Zaidenov V. A., Onishchenko N. A. Cell transplantation inhibits inflammatory reaction and stimulates repair processes in burn wound. Bulletin of Experimental Biology and Medicine. 2006;142(1):112–115. doi: 10.1007/s10517-006-0306-x.
    1. Rustad K. C., Wong V. W., Sorkin M., et al. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials. 2012;33(1):80–90. doi: 10.1016/j.biomaterials.2011.09.041.
    1. Sasaki M., Abe R., Fujita Y., Ando S., Inokuma D., Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. The Journal of Immunology. 2008;180(4):2581–2587. doi: 10.4049/jimmunol.180.4.2581.
    1. Sheng Z., Fu X., Cai S., et al. Regeneration of functional sweat gland-like structures by transplanted differentiated bone marrow mesenchymal stem cells. Wound Repair and Regeneration. 2009;17(3):427–435. doi: 10.1111/j.1524-475X.2009.00474.x.
    1. Shumakov V. I., Onishchenko N. A., Rasulov M. F., Krasheninnikov M. E., Zaidenov V. A. Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts. Bulletin of Experimental Biology and Medicine. 2003;136(2):192–195. doi: 10.1023/A:1026387411627.
    1. Stoff A., Rivera A. A., Banerjee N. S., et al. Promotion of incisional wound repair by human mesenchymal stem cell transplantation. Experimental Dermatology. 2009;18(4):362–369. doi: 10.1111/j.1600-0625.2008.00792.x.
    1. Tian H., Lu Y., Shah S. P., Hong S. 14S,21R-dihydroxydocosahexaenoic acid remedies impaired healing and mesenchymal stem cell functions in diabetic wounds. The Journal of Biological Chemistry. 2011;286(6):4443–4453. doi: 10.1074/jbc.m110.100388.
    1. Volk S. W., Radu A., Zhang L., Liechty K. W. Stromal progenitor cell therapy corrects the wound-healing defect in the ischemic rabbit ear model of chronic wound repair. Wound Repair and Regeneration. 2007;15(5):736–747. doi: 10.1111/j.1524-475X.2007.00277.x.
    1. Wu Y., Chen L., Scott P. G., Tredget E. E. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007;25(10):2648–2659. doi: 10.1634/stemcells.2007-0226.
    1. Yang M., Sheng L., Li H., Weng R., Li Q.-F. Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. Microsurgery. 2010;30(4):275–281. doi: 10.1002/micr.20779.
    1. Yeum C. E., Park E. Y., Lee S.-B., Chun H.-J., Chae G.-T. Quantification of MSCs involved in wound healing: use of SIS to transfer MSCs to wound site and quantification of MSCs involved in skin wound healing. Journal of Tissue Engineering and Regenerative Medicine. 2013;7(4):279–291. doi: 10.1002/term.521.
    1. Ko S. H., Nauta A., Wong V., Glotzbach J., Gurtner G. C., Longaker M. T. The role of stem cells in cutaneous wound healing: what do we really know? Plastic and Reconstructive Surgery. 2011;127(supplement 1):10S–20S.
    1. Bourin P., Bunnell B. A., Casteilla L., et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT) Cytotherapy. 2013;15(6):641–648. doi: 10.1016/j.jcyt.2013.02.006.
    1. Levi B., Longaker M. T. Concise review: adipose-derived stromal cells for skeletal regenerative medicine. Stem Cells. 2011;29(4):576–582. doi: 10.1002/stem.612.
    1. Galiano R. D., Michaels V J., Dobryansky M., Levine J. P., Gurtner G. C. Quantitative and reproducible murine model of excisional wound healing. Wound Repair and Regeneration. 2004;12(4):485–492. doi: 10.1111/j.1067-1927.2004.12404.x.
    1. Glotzbach J. P., Januszyk M., Vial I. N., et al. An information theoretic, microfluidic-based single cell analysis permits identification of subpopulations among putatively homogeneous stem cells. PLoS ONE. 2011;6(6) doi: 10.1371/journal.pone.0021211.e21211
    1. Januszyk M., Sorkin M., Glotzbach J. P., et al. Diabetes irreversibly depletes bone marrow-derived mesenchymal progenitor cell subpopulations. Diabetes. 2014;63(9):3047–3056. doi: 10.2337/db13-1366.
    1. Chung M. T., Liu C., Hyun J. S., et al. CD90 (Thy-1)-positive selection enhances osteogenic capacity of human adipose-derived stromal cells. Tissue Engineering Part A. 2013;19(7-8):989–997. doi: 10.1089/ten.tea.2012.0370.
    1. Mansilla E., Aquino V. D., Roque G., Tau J. M., MacEira A. Time and regeneration in burns treatment: heading into the first worldwide clinical trial with cadaveric mesenchymal stem cells. Burns. 2012;38(3):450–452. doi: 10.1016/j.burns.2011.09.007.
    1. Dabiri G., Heiner D., Falanga V. The emerging use of bone marrow-derived mesenchymal stem cells in the treatment of human chronic wounds. Expert Opinion on Emerging Drugs. 2013;18(4):405–419. doi: 10.1517/14728214.2013.833184.
    1. Wong V. W., Rustad K. C., Galvez M. G., et al. Engineered pullulan-collagen composite dermal hydrogels improve early cutaneous wound healing. Tissue Engineering Part A. 2011;17(5-6):631–644.
    1. Clover A. J., Kumar A. H., Isakson M., et al. Allogeneic mesenchymal stem cells, but not culture modified monocytes, improve burn wound healing. Burns. 2015;41(3):548–557. doi: 10.1016/j.burns.2014.08.009.
    1. Wong V. W., Gurtner G. C., Longaker M. T. Wound healing: a paradigm for regeneration. Mayo Clinic Proceedings. 2013;88(9):1022–1031. doi: 10.1016/j.mayocp.2013.04.012.
    1. McArdle A., Lo D. D., Hyun J. S., et al. Discussion: a report of the ASPS task force on regenerative medicine: opportunities for plastic surgery. Plastic and Reconstructive Surgery. 2013;131(2):400–403. doi: 10.1097/prs.0b013e318278d88c.
    1. Whelan D., Caplice N. M., Clover A. J. Fibrin as a delivery system in wound healing tissue engineering applications. Journal of Controlled Release. 2014;196C:1–8.
    1. Rasulov M. F., Vasilchenkov A. V., Onishchenko N. A., et al. First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns. Bulletin of Experimental Biology and Medicine. 2005;139(1):141–144. doi: 10.1007/s10517-005-0232-3.
    1. Nambu M., Kishimoto S., Nakamura S., et al. Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix. Annals of Plastic Surgery. 2009;62(3):317–321. doi: 10.1097/SAP.0b013e31817f01b6.
    1. Sasaki M., Abe R., Fujita Y., Ando S., Inokuma D., Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. Journal of Immunology. 2008;180(4):2581–2587. doi: 10.4049/jimmunol.180.4.2581.
    1. Nauta A., Seidel C., Deveza L., et al. Adipose-derived stromal cells overexpressing vascular endothelial growth factor accelerate mouse excisional wound healing. Molecular Therapy. 2013;21(2):445–455. doi: 10.1038/mt.2012.234.
    1. Badiavas E. V., Falanga V. Treatment of chronic wounds with bone marrow-derived cells. Archives of Dermatology. 2003;139(4):510–516. doi: 10.1001/archderm.139.4.510.
    1. Dash N. R., Dash S. N., Routray P., Mohapatra S., Mohapatra P. C. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Research. 2009;12(5):359–366. doi: 10.1089/rej.2009.0872.
    1. Yoshikawa T., Mitsuno H., Nonaka I., et al. Wound therapy by marrow mesenchymal cell transplantation. Plastic and Reconstructive Surgery. 2008;121(3):860–877. doi: 10.1097/01.prs.0000299922.96006.24.
    1. Rasulov M. F., Sevast'ianov V. I., Egorova V. A., et al. A comparative study of the dynamics of deep burns healing in using medullary allogenic fibroblast-like mesenchymal stem cells from bone marrow immobilized on biodegrading membranes or taken from cultural plastic. Patologicheskaia Fiziologiia i Eksperimental'naia Terapiia. 2005;(2):20–23.
    1. Yoshikawa T., Mitsuno H., Nonaka I., et al. Wound therapy by marrow mesenchymal cell transplantation. Plastic and Reconstructive Surgery. 2008;121(3):860–877.
    1. Siev-Ner I. Safety Study of Stem Cells Treatment in Diabetic Foot Ulcers. 2012. .
    1. Falanga V. Study of the Effectiveness of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Fibrin to Treat Chronic Wounds. 2012. .
    1. Baksh D., Song L., Tuan R. S. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. Journal of Cellular and Molecular Medicine. 2004;8(3):301–316. doi: 10.1111/j.1582-4934.2004.tb00320.x.
    1. Ma K., Laco F., Ramakrishna S., Liao S., Chan C. K. Differentiation of bone marrow-derived mesenchymal stem cells into multi-layered epidermis-like cells in 3D organotypic coculture. Biomaterials. 2009;30(19):3251–3258. doi: 10.1016/j.biomaterials.2009.02.025.
    1. Li H. H., Fu X. Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration. Cell and Tissue Research. 2012;348(3):371–377. doi: 10.1007/s00441-012-1393-9.
    1. Galindo L. T., Filippo T. R. M., Patricia S., et al. Mesenchymal stem cell therapy modulates the inflammatory response in experimental traumatic brain injury. Neurology Research International. 2011;2011:9. doi: 10.1155/2011/564089.564089
    1. Yoon B. S., Moon J.-H., Jun E. K., et al. Secretory profiles and wound healing effects of human amniotic fluid-derived mesenchymal stem cells. Stem Cells and Development. 2010;19(6):887–902. doi: 10.1089/scd.2009.0138.
    1. Mansilla E., Marin G. H., Sturla F., et al. Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplantation Proceedings. 2005;37(1):292–294. doi: 10.1016/j.transproceed.2005.01.070.
    1. Senarath-Yapa K., McArdle A., Renda A., Longaker M. T., Quarto N. Adipose-derived stem cells: a review of signaling networks governing cell fate and regenerative potential in the context of craniofacial and long bone skeletal repair. International Journal of Molecular Sciences. 2014;15(6):9314–9330. doi: 10.3390/ijms15069314.
    1. Cai S., Pan Y., Han B., Sun T.-Z., Sheng Z.-Y., Fu X.-B. Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands. Chinese Medical Journal. 2011;124(15):2260–2268. doi: 10.3760/cma.j.issn.0366-6999.2011.15.004.
    1. Fu X.-B., Fang L.-J., Wang Y.-X., Sun T.-Z., Cheng B. Enhancing the repair quality of skin injury on porcine after autografting with the bone marrow mesenchymal stem cells. Zhonghua Yi Xue Za Zhi. 2004;84(11):920–924.
    1. Zhang C., Ha X.-Q., Liu Y., Jin L.-J., Lü T.-D. Bone marrow mesenchymal stem cells transfected with hepatocyte growth factor gene for repair of burn wound after allotransplantation. Journal of Clinical Rehabilitative Tissue Engineering Research. 2008;12(51):10134–10138.
    1. Sheng Z., Fu X., Cai S., et al. Regeneration of functional sweat gland-like structures by transplanted differentiated bone marrow mesenchymal stem cells. Wound Repair and Regeneration. 2009;17(3):427–435. doi: 10.1111/j.1524-475x.2009.00474.x.
    1. Liu H., Li X.-Q., Chen W.-P., Xiang H.-X., Hu J., Zhang X.-W. Construction of tissue engineered skin by collagen with bone mesenchymal stem cells transfected with angiotensin I for repairing wound surface in scald models. Journal of Clinical Rehabilitative Tissue Engineering Research. 2009;13(15):2859–2864. doi: 10.3969/j.issn.1673-8225.2009.15.012.
    1. McArdle A., Senarath-Yapa K., Walmsley G. G., et al. The role of stem cells in aesthetic surgery: fact or fiction? Plastic and Reconstructive Surgery. 2014;134(2):193–200. doi: 10.1097/PRS.0000000000000404.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera