Recent progress in immunomodulatory mechanisms of mesenchymal stem cells in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

ZhangWei ,  ChenSong

Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, China;

Corresponding author：

ChenSong, Email: chensong20@hotmail.com

Keywords：

Diabetic retinopathy/physiopathology; Mesenchymal stem cells; T-lymphocytes, regulatory; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.02.028

Video：

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Diabetic retinopathy (DR) isacommon cause of blindness, its occurrence and development are the synergic results of multiple factors. Current studies suggest that inflammation and inflammatory factor has an important role in the pathogenesis of DR. The occurrence and development of DR are closely related with interleukins, intercellular adhesion molecules, hasten factors, tumor necrosis factor, C-reactive protein etc. Mesenchymal stem cells (MSCs) are pluripotent cells derived from the mesoderm and have multiple differentiation potentials, and anti-inflammatory and immunosuppressive function. Recent studies shown that MSCs transplantation can protect damaged retina by inflammatory regulation, which becomeanew research direction for DR treatment.

Citation： ZhangWei, ChenSong. Recent progress in immunomodulatory mechanisms of mesenchymal stem cells in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2016, 32(2): 221-224. doi: 10.3760/cma.j.issn.1005-1015.2016.02.028 Copy

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2.	Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. DOI: 10.1016/j.preteyeres.2011.05.002.
3.	Si YL, Zhao YL, Hao HJ, et al. MSCs: biological characteristics, clinical applications and their outstanding concerns[J]. Ageing Res Rev, 2011,10(1):93-103. DOI: 10.1016/j.arr.2010.08.005.
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5.	黎晓新.糖尿病视网膜病变的防治策略[J].中华眼科杂志,2008,44(1):6-8. DOI: 10.3321/j.issn:0412-4081.2008.01.003.Li XX.The strategy for the prevention of diabetic blindness[J].ChinJ Ophthalmol,2008,44(1):6-8.DOI: 10.3321/j.issn:0412-4081.2008.01.003.
6.	Arden GB, Sivaprasad S. Hypoxia and oxidative stress in the causation of diabetic retinopathy[J]. Curr Diabetes Rev,2011,7(5):291-304.
7.	Naudi A, Jove M, Ayala V, et al. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress[J/OL].Exp Diabetes Res, 2012,2012:696215[2012-01-02].http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255456/.DOI: 10.1155/2012/696215.
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9.	Chen H, Wen F, Zhang X,et al. Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy[J].Mol Vis, 2012,18:219-226.
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11.	Nguyen DV, Shaw LC, Grant MB. Inflammation in the pathogenesis of microvascular complications in diabetes[J].Front Endocrinol (Lausanne),2012,3:170. DOI: 10.3389/fendo.2012.00170.
12.	Brouwers O, Niessen PM, Ferreira I, et al. Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats[J].J Biol Chem,2011,286(2):1374-1380.DOI: 10.1074/jbc.M110.144097.
13.	Soleymaninejadian E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: cytokines and factors[J]. AmJReprod Immunol,2012, 67(1):1-8. DOI: 10.1111/j.1600-0897.2011.01069.
14.	Peck A, Mellins ED. Plasticity of T-cell phenotype and function: theThelper type 17 example[J].Immunology,2010,29(2):147-153.DOI: 10.1111/j.1365-2567. 2009.03189.x.
15.	De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications[J]. Curr Mol Med,2012,12(5):574-591.
16.	Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications[J]. Arch Pharm Res,2012,35(2):213-221.DOI: 10.1007/s12272-012-0202-z.
17.	Lotfinegad P, Shamsasenjan K, Movassaghpour A, et al.Immunomodulatory nature and site specific affinity of mesenchymal stem cells:ahope in cell therapy[J]. Adv Pharm Bull,2014,4(1):5-13.DOI: 10.5681/apb.2014.002.
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20.	Suva D, Passweg J, Arnaudeau S, et al. In vitro activated humanTlymphocytes very efficiently attach to allogenic multipotent mesenchymal stromal cells and transmigrate under them[J].J Cell Physiol,2008,214(3):588-594.
21.	Munir H, McGettrick HM. Mesenchymal stem cell therapy for autoimmune disease: risks and rewards[J].Stem Cells Dev,2015,24(18):2091-100. DOI: 10.1089/scd. 2015.0008.
22.	Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats[J]. Graefe′s Arch Clin Exp Ophthalmol, 2010,248(10):1415-1422.DOI: 10.1007/s00417-010-1384-z.
23.	Barradas AM, Monticone V, Hulsman M, et al. Molecular mechanisms of biomaterial-driven osteogenic differentiation in human mesenchymal stromal cells[J]. Integr Biol (Camb),2013, 24,5(7):920-931. DOI: 10.1039/c3ib40027a.
24.	Scalinci SZ, Scorolli L, Corradetti G, et al.Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes: neuroprotective growth factors in the vitreous[J]. Clin Ophthalmol,2011,5:691-696. DOI: 10.2147/OPTH.S21161.
25.	Ezquer ME, Ezquer FE, Arango-Rodríguez ML, et al. MSC transplantation:apromising therapeutic strategy to manage the onset and progression of diabetic nephropathy[J]. Biol Res, 2012, 45(3):289-296.DOI: 10.4067/S0716-97602012000300010.
26.	Xu Y, Gu Z, Shen B, et al. Roles of Wnt/β-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice[J].JMol Neurosci, 2013, 49(2):250-261.DOI: 10.1007/s12031- 012- 9917-z.
27.	Yu Q, Liu L, Duan Y, et al. Wnt/β-catenin signaling regulates neuronal differentiation of mesenchymal stem cells[J]. Biochem Biophys Res Commun, 2013, 439(2):297-302. DOI: 10.1016/j.bbrc.2013.08.030.
28.	Volarevic V, Arsenijevic N, Lukic ML, et al. Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus[J]. Stem Cells, 2011, 29(1):5-10. DOI: 10.1002/stem.556.
29.	Dang Y, Zhang C, Zhu Y. Stem cell therapies for age-related macular degeneration: the past, present, and future[J]. Clin Interv Aging,2015,10:255-264. DOI: 10.2147/CIA.S73705.
30.	毕雪, 陈松, 林锦镛, 等. 不同途径移植人脐带间充质干细胞对糖尿病大鼠视网膜病变的影响[J]. 中华眼底病杂志, 2014, 30(2): 166-170. DOI: 10.3760/cma.j.issn. 1005-1015.2014.02.012.Bi X,Chen S,Lin JY,et al.Systemic and ocular transplantation of human umbilical cord mesenchymal stem cells into rats with diabetic retinopathy[J].ChinJOcul Fundus Dis,2014, 30(2): 166-170. DOI: 10.3760/cma.j.issn.1005-1015. 2014. 02. 012.
31.	Tzameret A, Sher I, Belkin M,et al. Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function inarat model of retinal degeneration[J]. Stem Cell Res, 2015,15(2):387-394. DOI: 10.1016/j. Scr. 2015.08.007.

1. Barber AJ, Gardner TW, Abcouwer SF. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy[J]. Invest Ophthalmol Vis Sci,2011,52(2):1156-1163. DOI: 10.1167/iovs.10-6293.
2. Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. DOI: 10.1016/j.preteyeres.2011.05.002.
3. Si YL, Zhao YL, Hao HJ, et al. MSCs: biological characteristics, clinical applications and their outstanding concerns[J]. Ageing Res Rev, 2011,10(1):93-103. DOI: 10.1016/j.arr.2010.08.005.
4. Gao F, Chiu SM, Motan DA, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects[J].Cell Death Dis,2016,7:2062.DOI: 10.1038/cddis.2015.327.
5. 黎晓新.糖尿病视网膜病变的防治策略[J].中华眼科杂志,2008,44(1):6-8. DOI: 10.3321/j.issn:0412-4081.2008.01.003.Li XX.The strategy for the prevention of diabetic blindness[J].ChinJ Ophthalmol,2008,44(1):6-8.DOI: 10.3321/j.issn:0412-4081.2008.01.003.
6. Arden GB, Sivaprasad S. Hypoxia and oxidative stress in the causation of diabetic retinopathy[J]. Curr Diabetes Rev,2011,7(5):291-304.
7. Naudi A, Jove M, Ayala V, et al. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress[J/OL].Exp Diabetes Res, 2012,2012:696215[2012-01-02].http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255456/.DOI: 10.1155/2012/696215.
8. 许迅.糖尿病视网膜病变的早期防治[J]. 中华眼科杂志, 2008, 44(1):9-11. DOI: 10.3321/j.issn:0412-4081.2008.01.004.Xu X.Emphasizing the early prevention and treatment for diabetic retinopathy[J].ChinJOphthalmol,2008, 44(1):9-11.DOI: 10.3321/j. issn: 0412- 4081.2008.01.004.
9. Chen H, Wen F, Zhang X,et al. Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy[J].Mol Vis, 2012,18:219-226.
10. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effectorTcells develop viaalineage distinct from theThelper type 1 and 2 lineages[J]. Nat Immunol,2005,6(11):1123-1132.
11. Nguyen DV, Shaw LC, Grant MB. Inflammation in the pathogenesis of microvascular complications in diabetes[J].Front Endocrinol (Lausanne),2012,3:170. DOI: 10.3389/fendo.2012.00170.
12. Brouwers O, Niessen PM, Ferreira I, et al. Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats[J].J Biol Chem,2011,286(2):1374-1380.DOI: 10.1074/jbc.M110.144097.
13. Soleymaninejadian E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: cytokines and factors[J]. AmJReprod Immunol,2012, 67(1):1-8. DOI: 10.1111/j.1600-0897.2011.01069.
14. Peck A, Mellins ED. Plasticity of T-cell phenotype and function: theThelper type 17 example[J].Immunology,2010,29(2):147-153.DOI: 10.1111/j.1365-2567. 2009.03189.x.
15. De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications[J]. Curr Mol Med,2012,12(5):574-591.
16. Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications[J]. Arch Pharm Res,2012,35(2):213-221.DOI: 10.1007/s12272-012-0202-z.
17. Lotfinegad P, Shamsasenjan K, Movassaghpour A, et al.Immunomodulatory nature and site specific affinity of mesenchymal stem cells:ahope in cell therapy[J]. Adv Pharm Bull,2014,4(1):5-13.DOI: 10.5681/apb.2014.002.
18. Kalekar LA, Schmiel SE, Nandiwada SL, et al. CD4(+)Tcell anergy prevents autoimmunity and generates regulatoryTcell precursors[J]. Nat Immunol, 2016,17(3):304-314.DOI: 10.1038/ni.3331.
19. Hernandez AL, Kitz A, Wu C, et al. Sodium chloride inhibits the suppressive function of FOXP3+ regulatoryTcells[J].JClin Invest,2015,125(11):4212-4222. DOI: 10.1172/JCI81151.
20. Suva D, Passweg J, Arnaudeau S, et al. In vitro activated humanTlymphocytes very efficiently attach to allogenic multipotent mesenchymal stromal cells and transmigrate under them[J].J Cell Physiol,2008,214(3):588-594.
21. Munir H, McGettrick HM. Mesenchymal stem cell therapy for autoimmune disease: risks and rewards[J].Stem Cells Dev,2015,24(18):2091-100. DOI: 10.1089/scd. 2015.0008.
22. Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats[J]. Graefe′s Arch Clin Exp Ophthalmol, 2010,248(10):1415-1422.DOI: 10.1007/s00417-010-1384-z.
23. Barradas AM, Monticone V, Hulsman M, et al. Molecular mechanisms of biomaterial-driven osteogenic differentiation in human mesenchymal stromal cells[J]. Integr Biol (Camb),2013, 24,5(7):920-931. DOI: 10.1039/c3ib40027a.
24. Scalinci SZ, Scorolli L, Corradetti G, et al.Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes: neuroprotective growth factors in the vitreous[J]. Clin Ophthalmol,2011,5:691-696. DOI: 10.2147/OPTH.S21161.
25. Ezquer ME, Ezquer FE, Arango-Rodríguez ML, et al. MSC transplantation:apromising therapeutic strategy to manage the onset and progression of diabetic nephropathy[J]. Biol Res, 2012, 45(3):289-296.DOI: 10.4067/S0716-97602012000300010.
26. Xu Y, Gu Z, Shen B, et al. Roles of Wnt/β-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice[J].JMol Neurosci, 2013, 49(2):250-261.DOI: 10.1007/s12031- 012- 9917-z.
27. Yu Q, Liu L, Duan Y, et al. Wnt/β-catenin signaling regulates neuronal differentiation of mesenchymal stem cells[J]. Biochem Biophys Res Commun, 2013, 439(2):297-302. DOI: 10.1016/j.bbrc.2013.08.030.
28. Volarevic V, Arsenijevic N, Lukic ML, et al. Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus[J]. Stem Cells, 2011, 29(1):5-10. DOI: 10.1002/stem.556.
29. Dang Y, Zhang C, Zhu Y. Stem cell therapies for age-related macular degeneration: the past, present, and future[J]. Clin Interv Aging,2015,10:255-264. DOI: 10.2147/CIA.S73705.
30. 毕雪, 陈松, 林锦镛, 等. 不同途径移植人脐带间充质干细胞对糖尿病大鼠视网膜病变的影响[J]. 中华眼底病杂志, 2014, 30(2): 166-170. DOI: 10.3760/cma.j.issn. 1005-1015.2014.02.012.Bi X,Chen S,Lin JY,et al.Systemic and ocular transplantation of human umbilical cord mesenchymal stem cells into rats with diabetic retinopathy[J].ChinJOcul Fundus Dis,2014, 30(2): 166-170. DOI: 10.3760/cma.j.issn.1005-1015. 2014. 02. 012.
31. Tzameret A, Sher I, Belkin M,et al. Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function inarat model of retinal degeneration[J]. Stem Cell Res, 2015,15(2):387-394. DOI: 10.1016/j. Scr. 2015.08.007.

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