The influence of human umbilical cord mesenchymal stem cells transplanted into the tail vein of diabetic rats on apoptosis of retinal neurons and the retinal expression of glial fibrillary acidic protein_Chinese Journal of Ocular Fundus Diseases

Authors：

Song Tianling ,  Meng Xuxia , Cao Bowen , Guo Qingmin , Zhou Xianhui , Hu Die

Department of Ophthalmology, The Affiliated of Qingdao University, Qingdao 266500, China (Zhou Xianhui, now working at the Department of Ophthalmology, Yantai YeDa Hospital; Hu Die, now working at the Qingdao Eye Hospital);

Corresponding author：

Meng Xuxia, Email: mengxuxia@163.com

Keywords：

Diabetic retinopathy; Mesenchymal stem cells; Neurons; Apoptosis

DOI：

10.3760/cma.j.issn.1005-1015.2018.02.013

Video：

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Objective To observe the influence of human umbilical cord mesenchymal stem cells (hUCMSC) transplanted into the tail vein of diabetic rats on apoptosis of retinal neurons and the retinal expression level of glial fibrillary acidic protein (GFAP). Methods Seventy clean male Sprague-Dawley rats were randomly divided into the normal control group (group A), diabetes mellitus (DM) only group (group B), DM + balanced salt solution (BSS) group (group C), DM + hUCMSC group (group D), with 10 rats in each group. DM rats were induced by intraperitoneal injection of streptozotocin. Apoptosis of retinal cells was assayed by dUTP nick end labeling. Immunohistochemistry and Western blot was performed to detect the retinal expressions of GFAP in rats. Results Compared with group A, large numbers of apoptotic cells could be found in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) of group B and group C, however the apoptotic cells in group D were significantly reduced than group B and C. The expression of GFAP was mainly located in the retinal GCL and retinal nerve fibre layer (RNFL) in group A, throughout the inner plexiform layer (IPL) in group B and C, only distributed in RNFL and GCL in group D. It was obvious that the expression of GFAP in group B and C was higher than group A. Compared with group B and C, the expression of GFAP in group D was significantly reduced. The difference of GFAP expression among the 4 groups was significant (F=79.635, P<0.05). Conclusion hUCMSC could inhibit the apoptosis of retinal cells and activation of glial cells in early DM rats.

Citation： Song Tianling, Meng Xuxia, Cao Bowen, Guo Qingmin, Zhou Xianhui, Hu Die. The influence of human umbilical cord mesenchymal stem cells transplanted into the tail vein of diabetic rats on apoptosis of retinal neurons and the retinal expression of glial fibrillary acidic protein. Chinese Journal of Ocular Fundus Diseases, 2018, 34(2): 164-167. doi: 10.3760/cma.j.issn.1005-1015.2018.02.013 Copy

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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. Hao M, Li Y, Kuang H, et al. Estrogen prevents high-glucose-induced damage of retinal ganglion cells via mitochondrial pathway[J]. Graefe’s Arch Clin Exp Ophthalmol, 2015, 253(1): 83-90. DOI: 10.1007/s00417-014-2771-7.
3. 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.
4. Woher JR.Diabetic retinopathy[J].Ophthalmol, 1961, 51:1123-1141.
5. Barber AJ, Lieth E, Khin SA, et al.Neural apoptosis in the retina during experimental and human diabetes:early onset and effect of insulin[J].J Clin Invest, 1998, 102(4): 783-791.
6. Coughlin BA , Feenstra DJ , Mohr S. Müller cells and diabetic retinopathy[J]. Vision Res, 2017, 139:93-100. DOI: 10.1016/j.visres.2017.03.013.
7. Tenckhoff S, Hollborn M, Kohen L, et al.Diversity of aquaporin mRNA expressed by rat and human retinas[J].Neuroreport, 2005, 16(1): 53-56.
8. Jiang Y, Jahagirdar BN, Reinhardt RL.Pluripotency of mesenchymal stem cells derived from adult marrow[J].Nature, 2002, 418(6893): 41-49.DOI:10.1038/nature00870.
9. Dong L, Pu Y, Zhang L, et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410[J]. Cell Death Dis, 2018, 9(2): 218. DOI: 10.1038/s41419-018-0323-5.
10. Wang H, Qiu X, Ni P, et al. Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats[J].Int J Mol Med, 2014, 33(2): 263-270. DOI: 10.3892/ijmm.2013.1572.
11. Ringe J, Strassburg S, Neumann K, et al. Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2[J]. Cell Biochem, 2007, 101(1): 135-146.
12. 张惟, 陈松, 王继明, 等.人脐带间充质干细胞向神经细胞分化的实验研究[J].临床眼科杂志, 2015, 23(4): 365-370.DOI:10.3969/j.issn.1006-8422.2015.04.027.Zhang W, Chen S, Wang JM, et al.Differentiation of human umbilical cord mesenchymal stem cell to neural cells[J].J Clin Ophthalmol, 2015, 23(4): 365-370.DOI:10.3969/j.issn.1006-8422.2015.04.027.
13. Hsieh JY, Wang HW, Chang SJ, et al.Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis[J/OL]. PLoS One, 2013, 8(8): 72604[2013-08-22].https://doi.org/10.1371/journal.pone.0072604. DOI:10.1371/journal.pone.0072604.
14. Scalinci SZ, Scorolli I, 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.
15. Zhang W, Wang Y, Kong J, et al. Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy[J].Sci Rep, 2017, 7(1): 408. DOI:10.1038/s41598-017-00298-2.
16. Ankrum J, Karp JM.Mesenchymal stem cell therapy: two steps forward, one step back[J]. Trends Mol Med, 2010, 16(5): 203-209.DOI:10.1016/j.molmed.2010.02.005.
17. Gao X, Song L, Shen K, et al.Bone marrow mesenchymal stem cells promote the repair of islets from diabetic mice through paracrine actions[J].Mol Cell Endocrinol, 2014, 388(1-2): 41-50. DOI:10.1016/j.mce.2014.03.004.
18. Liao Y.Allogeneic cord blood mesenchymal stem cell transplantation for treating Emery-Dreifus muscular dystrophy in one case[J].J Clin Rehabilitative Tissue Eng Res, 2009, 13(27): 5393-5396.
19. Sun L, Wang D, Liang J, et al.Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus[J]. Arthritis Rheum, 2010, 62(8): 2467-2475. DOI: 10.1002/art.27548.

Chinese Journal of Ocular Fundus Diseases

The influence of human umbilical cord mesenchymal stem cells transplanted into the tail vein of diabetic rats on apoptosis of retinal neurons and the retinal expression of glial fibrillary acidic protein

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