Mesenchymal stem cells for diabetic foot: existing problems and better application

doi:10.3969/j.issn.2095-4344.0425

Abstract

Abstract:

BACKGROUND: Diabetic foot is a common chronic complication of diabetes, and an increasing risk of amputation is found in such patients. The current common treatments include control of blood glucose, debridement of local tissues, anti-infection and revascularization, but none of them has achieved ideal curative effects. Further investigation on more effective treatment is needed. Recent studies have shown that mesenchymal stem cells can promote the healing of diabetic foot and improve the clinical symptoms.
OBJECTIVE: To review the mechanism and clinical application of mesenchymal stem cells in the treatment of diabetic foot.
METHODS: The first author searched the relevant literature (original articles and reviews) published in the PubMed and CNKI databases from 2012 to 2017, using the keywords of “mesenchymal stem cell, diabetic foot” in English and Chinese, respectively. After excluding irrelevant articles or those out of date, 44 articles fulfilling the inclusive criteria were reviewed.
RESULTS AND CONCLUSION: Mesenchymal stem cells regardless of source are a promising and effect therapy for diabetic foot. Bone marrow mesenchymal stem cells have no immune limitation and are the most effective via intramuscular injection. Umbilical cord blood derived mesenchymal stem cells have some advantages, such as rich sources, short doubling time, long survival time. Adipose derived mesenchymal stem cells are widely distributed and can be easily isolated and extracted. Placenta derived mesenchymal stem cells have good proliferation ability, which are the most effective via intraperitoneal injection. Among them, bone marrow mesenchymal stem cells may be the best choice for diabetic foot treatment.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Stem Cells, Tissue Engineering, Diabetes Mellitus

CLC Number:

R394.2

Xiang Jie, Zhang Jie. Mesenchymal stem cells for diabetic foot: existing problems and better application[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(1): 146-151.

Figures/Tables 1

References

[1] Ibrahim A. IDF Clinical practice recommendation on the diabetic foot: a guide for healthcare professionals. Diabetes Res Clin Pract. 2017;127:285-287.

[2] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中华内分泌代谢杂志,2014,30(10):26-89.

[3] Jiang Y, Ran X, Jia L, et al. Epidemiology of type 2 diabetic foot problems and predictive factors for amputation in China. Int J Low Extrem Wounds. 2015; 14(1):19-27.

[4] Brod M, Nikolajsen A, Weatherall J, et al. The Economic Burden of Post-prandial Hyperglycemia (PPH) Among People with Type 1 and Type 2 Diabetes in Three Countries. Diabetes Ther. 2016;7(1):75-90.

[5] 中国医疗保健国际交流促进会糖尿病足病分会.中国糖尿病足诊治指南[J].中华医学杂志,2017,97(4):251-258.

[6] Zhao QS, Xia N, Zhao N, et al. Localization of human mesenchymal stem cells from umbilical cord blood and their role in repair of diabetic foot ulcers in rats. Int J Biol Sci. 2013;10(1):80-89.

[7] Li S, Wang X, Li J, et al. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells. Stem Cells Int. 2016;2016:5896061.

[8] Maxson S, Lopez EA, Yoo D, et al. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med. 2012;1(2):142-149.

[9] Marfia G, Navone SE, Di Vito C, et al. Mesenchymal stem cells:potential for therapy and treatment of chronic non-healing skin wounds. Organogenesis. 2015;11(4):183-206.

[10] El-Demerdash RF, Hammad LN, Kamal MM, et al. A comparison of Wharton's jelly and cord blood as a source of mesenchymal stem cells for diabetes cell therapy. Regen Med. 2015;10(7):841-855.

[11] Rani S, Ryan AE, Griffin MD, et al. Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Mol Ther. 2015; 23(5):812-823.

[12] Marrotte EJ, Chen DD, Hakim JS, et al. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice. J Clin Invest. 2010;120(12):4207-4219.

[13] Chen S, Shi J, Zhang M, et al. Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing. Sci Rep. 2015;5:18104.

[14] Schiavetta A, Maione C, Botti C, et al. A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the naples and pietra ligure evaluation of stem cells study. Stem Cells Transl Med. 2012; 1(7):572-578.

[15] Hua J, Gong J, Meng H, et al. Comparison of different methods for the isolation of mesenchymal stem cells from umbilical cord matrix: proliferation and multilineage differentiation as compared to mesenchymal stem cells from umbilical cord blood and bone marrow. Cell Biol Int. 2013; 38(2):198-210.

[16] Kato J, Kamiya H, Himeno T, et al. Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats. J Diabetes Complications. 2014;28(5):588-595.

[17] Wan J, Xia L, Liang W, et al. Transplantation of bone marrow-derived mesenchymal stem cells promotes delayed wound healing in diabetic rats. J Diabetes Res. 2013;2013(9): 647107.

[18] O'Loughlin A, Kulkarni M, Creane M, et al. Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer. Diabetes. 2013;62(7):2588-2594.

[19] 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.

[20] Zhang QZ, Su WR, Shi SH, et al. Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells. 2010;28(10):1856-1868.

[21] Xu J, Wu W, Zhang L, et al. The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment. Diabetes. 2012;61(11):2906-2912.

[22] Li M, Zhao Y, Hao H, et al. Mesenchymal stem cell-conditioned medium improves the proliferation and migration of keratinocytes in a diabetes-like microenvironment. Int J Low Extrem Wounds. 2015;14(1):73-86.

[23] Iwamoto S, Lin X, Ramirez R, et al. Bone marrow cell mobilization by the systemic use of granulocyte colony-stimulating factor (GCSF) improves wound bed preparation. Int J Low Extrem Wounds. 2013;12(4):256-264.

[24] Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci. 2013;14(9):17986-18001.

[25] You HJ, Namgoong S, Han SK, et al. Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro-a pilot study. Cytotherapy. 2015;17(11):1506-1513.

[26] Xia N, Xu JM, Zhao N, et al. Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats. Neurosci Lett. 2015;597:84-89.

[27] Elsharawy MA, Naim M, Greish S. Human CD34+ stem cells promote healing of diabetic foot ulcers in rats.Interactive Cardiovascular and Thoracic Surgery. 2012;14(3):288-293.

[28] Maharlooei MK, Bagheri M, Solhjou Z, et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Res Clin Pract. 2011;93(2):228-234.

[29] Kim SW, Zhang HZ, Guo L, et al. Amniotic Mesenchymal Stem Cells Enhance Wound Healing in Diabetic NOD/SCID Mice through High Angiogenic and Engraftment Capabilities. PLoS One. 2012;7(7):e41105.

[30] Kuo YR, Wang CT, Cheng JT, et al. Adipose-derived Stem Cells Accelerate Diabetic Wound Healing through the Induction of Autocrine and Paracrine Effects. Cell Transplant. 2016;25(1):71-81.

[31] Nie C, Yang D, Xu J, et al. Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplant. 2011; 20(2):205-216.

[32] Kato Y, Iwata T, Morikawa S, et al. Allogeneic transplantation of an adipose-derived stem cell (ASC) sheet combined with artificial skin accelerates wound healing in a rat wound model of type 2 diabetes and obesity. Diabetes. 2015;64(8): 2723-2734.

[33] Amos PJ, Kapur SK, Stapor PC, et al. Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery. Tissue Eng Part A. 2010;16(5):1595-1606.

[34] Abd-Allah SH, El-shal AS, Shalaby SM, et al. The role of placenta-derived mesenchymal stem cells in healing of induced full-thickness skin wound in a mouse model. IUBMB Life. 2015;67(9):701-709.

[35] Kong P, Xie X, Li F, et al. Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats.Biochem Biophys Res Commun. 2013;438(2):410-419.

[36] Wang H, Chen L, Liu Y, et al. Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation.Am J Transl Res. 2016; 8(11):4912-4921.

[37] Skardal A, Mack D, Kapetanovic E, et al. Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl Med. 2012;1(11):792-802.

[38] Jun EK, Zhang Q, Yoon BS, et al. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways. Int J Mol Sci. 2014;15(1):605-628.

[39] Nowak WN, Borys S, Kusinska K, et al. Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome. J Diabetes Investig. 2014;5(1):99-107.

[40] Mizukami H, Yagihashi S. Exploring a New Therapy for Diabetic Polyneuropathy–The Application of Stem Cell Transplantation. Front Endocrinol. 2014;5:45.

[41] Lau TT, Wang DA. Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert Opin Biol Ther. 2011;11(2):189-197.

[42] Liu N, Tian J, Jin C, et al. Migration of CXCR4 gene-modified bone marrow-derived mesenchymal stem cells to the acute kidney injury.J Cell Biochem. 2013;114(12):2677-2689.

[43] Lu D, Chen B, Liang Z, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011;92(1):26-36.

[44] Yang SS, Kim NR, Park KB, et al. A phase I study of human cord blood-derived mesenchymal stem cell therapy in patients with peripheral arterial occlusive disease. Int J Stem Cells. 2013;6(1):37-44.