Preliminary research on the effects and mechanisms of umbilical cord‑derived mesenchymal stem cells in streptozotocin‑induced diabetic retinopathy Corrigendum in /10.3892/ijmm.2020.4708

Zhao,Ken; Liu,Jie; Dong,Gang; Xia,Huan; Wang,Pingan; Xiao,Xuan; Chen,Zhen

doi:10.3892/ijmm.2020.4623

Preliminary research on the effects and mechanisms of umbilical cord‑derived mesenchymal stem cells in streptozotocin‑induced diabetic retinopathy

Corrigendum in: /10.3892/ijmm.2020.4708

Authors:
- Ken Zhao
- Jie Liu
- Gang Dong
- Huan Xia
- Pingan Wang
- Xuan Xiao
- Zhen Chen
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Affiliations: Department of Ophthalmology, People's Hospital of Daye, The Second Affiliated Hospital of Hubei Polytechnic College, Daye, Hubei 435100, P.R. China, Wuhan Myhalic Biotechnology Co., Ltd., Wuhan, Hubei 430206, P.R. China, Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: June 1, 2020 https://doi.org/10.3892/ijmm.2020.4623
Pages: 849-858

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Abstract

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes, and a common cause of blindness in working‑age individuals. Mesenchymal stem cell (MSC) transplantation has been considered a promising intervention therapy for DR, wherein the differentiation of MSCs into nerve cells plays an essential role. However, research into the role of MSCs in DR treatment remains incomplete, and the mechanisms of retinal repair at the molecular level have yet to be clarified. In the present study, all‑trans retinoic acid (ATRA) was used to promote the proliferation of rat umbilical cord (UC)‑derived MSCs and their differentiation into nerve cells. Furthermore, the effects and mechanisms of UC‑MSCs with or without ATRA treatment were investigated in rats subjected to streptozocin (STZ)‑induced DR. The results demonstrated that the transplantation of UC‑MSCs treated with or without ATRA attenuated DR in rats, and alleviated retinal tissue damage and apoptosis. In addition, the transplantation of UC‑MSCs treated with or without ATRA attenuated angiogenesis and inflammation in the retina by regulating the levels of relevant cytokines. UC‑MSCs treated with ATRA exerted a more prominent therapeutic effect than the untreated UC‑MSCs. On the whole, these findings indicate that UC‑MSCs alleviate STZ‑induced DR in rats by regulating angiogenesis and the inflammatory response at the molecular level. Thus, the findings of the present study may provide a theoretical basis for the application of MSCs in the treatment of DR.

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1	Fiori A, Terlizzi V, Kremer H, Gebauer J, Hammes HP, Harmsen MC and Bieback K: Mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy. Immunobiology. 223:729–743. 2018. View Article : Google Scholar : PubMed/NCBI
2	Whiting DR, Guariguata L, Weil C and Shaw J: IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 94:311–321. 2011. View Article : Google Scholar : PubMed/NCBI
3	Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, et al: Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 35:556–564. 2012. View Article : Google Scholar : PubMed/NCBI
4	Selvaraj K, Gowthamarajan K, Karri VV, Barauah UK, Ravisankar V and Jojo GM: Current treatment strategies and nanocarrier based approaches for the treatment and management of diabetic retinopathy. J Drug Target. 25:386–405. 2017. View Article : Google Scholar : PubMed/NCBI
5	Zhang C, Xu Y, Tan HY, Li S, Wang N, Zhang Y and Feng Y: Neuroprotective effect of He-Ying-Qing-Re formula on retinal ganglion cell in diabetic retinopathy. J Ethnopharmacol. 214:179–189. 2018. View Article : Google Scholar
6	Ding DC, Shyu WC and Lin SZ: Mesenchymal stem cells. Cell Transplant. 20:5–14. 2011. View Article : Google Scholar : PubMed/NCBI
7	Nagamura-Inoue T and He H: Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility. World J Stem Cells. 6:195–202. 2014. View Article : Google Scholar : PubMed/NCBI
8	Gu X, Yu X, Zhao C, Duan P, Zhao T, Liu Y, Li S, Yang Z, Li Y, Qian C, et al: Efficacy and safety of autologous bone marrow mesenchymal stem cell transplantation in patients with diabetic retinopathy. Cell Physiol Biochem. 49:40–52. 2018. View Article : Google Scholar : PubMed/NCBI
9	Wang J, Zhang W, He GH, Wu B and Chen S: Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo. Int J Ophthalmol. 11:766–772. 2018.
10	Scalinci SZ, Scorolli L, Corradetti G, Domanico D, Vingolo EM, Meduri A, Bifani M and Siravo D: 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. Clin Ophthalmol. 5:691–696. 2011. View Article : Google Scholar : PubMed/NCBI
11	Yang Z, Li K, Yan X, Dong F and Zhao C: Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch Clin Exp Ophthalmol. 248:1415–1422. 2010. View Article : Google Scholar : PubMed/NCBI
12	Hsieh JY, Wang HW, Chang SJ, Liao KH, Lee IH, Lin WS, Wu CH, Lin WY and Cheng SM: Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One. 8:e726042013. View Article : Google Scholar : PubMed/NCBI
13	Zhang W, Wang Y, Kong J, Dong M, Duan H and Chen S: Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy. Sci Rep. 7:4082017. View Article : Google Scholar : PubMed/NCBI
14	Mottaghi S, Larijani B and Sharifi AM: Atorvastatin: An efficient step forward in mesenchymal stem cell therapy of diabetic retinopathy. Cytotherapy. 15:263–266. 2013. View Article : Google Scholar
15	Siddikuzzaman, Guruvayoorappan C and Berlin Grace VM: All trans retinoic acid and cancer. Immunopharmacol Immunotoxicol. 33:241–249. 2011. View Article : Google Scholar
16	Gong M, Bi Y, Jiang W, Zhang Y, Chen L, Hou N, Chen J and Li T: Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation. Int J Biochem Cell Biol. 45:866–875. 2013. View Article : Google Scholar : PubMed/NCBI
17	Tanaka K, Tamiya-Koizumi K, Hagiwara K, Ito H, Takagi A, Kojima T, Suzuki M, Iwaki S, Fujii S, Nakamura M, et al: Role of down-regulated neutral ceramidase during all-trans retinoic acid-induced neuronal differentiation in SH-SY5Y neuroblastoma cells. J Biochem. 151:611–620. 2012. View Article : Google Scholar : PubMed/NCBI
18	Murashov AK, Pak ES, Hendricks WA, Owensby JP, Sierpinski PL, Tatko LM and Fletcher PL: Directed differentiation of embryonic stem cells into dorsal interneurons. FASEB J. 19:252–254. 2005. View Article : Google Scholar
19	Xi J and Yang Z: Expression of RALDHs (ALDH1As) and CYP26s in human tissues and during the neural differentiation of P19 embryonal carcinoma stem cell. Gene Expr Patterns. 8:438–442. 2008. View Article : Google Scholar : PubMed/NCBI
20	Pourjafar M, Saidijam M, Etemadi K and Najafi R: All-trans retinoic acid enhances in vitro mesenchymal stem cells migration by targeting matrix metalloproteinases 2 and 9. Biotechnol Lett. 39:1263–1268. 2017. View Article : Google Scholar : PubMed/NCBI
21	Jin W, Xu YP, Yang AH and Xing YQ: In vitro induction and differentiation of umbilical cord mesenchymal stem cells into neuron-like cells by all-trans retinoic acid. Int J Ophthalmol. 8:250–256. 2015.PubMed/NCBI
22	Yin Y, Chen F, Wang W, Wang H and Zhang X: Resolvin D1 inhibits inflammatory response in STZ-induced diabetic retinopathy rats: Possible involvement of NLRP3 inflammasome and NF-κB signaling pathway. Mol Vis. 23:242–250. 2017.
23	Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O'Neal DN and Januszewski AS: Biomarkers in diabetic retinopathy. Rev Diabet Stud. 12:159–195. 2015. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	Xie X, Peng J, Huang K, Huang J, Shen X, Liu P and Huang H: Polydatin ameliorates experimental diabetes-induced fibronectin through inhibiting the activation of NF-κB signaling pathway in rat glomerular mesangial cells. Mol Cell Endocrinol. 362:183–193. 2012. View Article : Google Scholar : PubMed/NCBI
26	Fu X, Li S, Zhou S, Wu Q, Jin F and Shi J: Stimulatory effect of icariin on the proliferation of neural stem cells from rat hippo-campus. BMC Complement Altern Med. 18:342018. View Article : Google Scholar
27	Ding SSL, Subbiah SK, Khan MSA, Farhana A and Mok PL: Empowering mesenchymal stem cells for ocular degenerative disorders. Int J Mol Sci. 20:pii: E1784. 2019. View Article : Google Scholar
28	Yue X, Zhifeng G, Biyu S, Guofeng X, Tianqiu Z, Jinxia J, Jing X, Suzhe L, Man L, Wei T, et al: Roles of Wnt/β-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice. J Mol Neurosci. 49:250–261. 2013. View Article : Google Scholar
29	Wu W, Lei H, Shen J and Tang L: The role of netrin-1 in angiogenesis and diabetic retinopathy: A promising therapeutic strategy. Discov Med. 23:315–323. 2017.PubMed/NCBI
30	Gardlik R and Fusekova I: Pharmacologic therapy for diabetic retinopathy. Semin Ophthalmol. 30:252–263. 2015. View Article : Google Scholar
31	Khan AA, Rahmani AH and Aldebasi YH: Diabetic retinopathy: Recent updates on different biomarkers and some therapeutic agents. Curr Diabetes Rev. 14:523–533. 2018. View Article : Google Scholar
32	Zhang SX and Ma JX: Ocular neovascularization: Implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res. 26:1–37. 2007. View Article : Google Scholar
33	Boyer DS, Hopkins JJ, Sorof J and Ehrlich JS: Anti-vascular endothelial growth factor therapy for diabetic macular edema. Ther Adv Endocrinol Metab. 4:151–169. 2013. View Article : Google Scholar : PubMed/NCBI
34	Stewart MW: Anti-vascular endothelial growth factor drug treatment of diabetic macular edema: The evolution continues. Curr Diabetes Rev. 8:237–246. 2012. View Article : Google Scholar : PubMed/NCBI
35	Bahrami B, Hong T, Gilles MC and Chang A: Anti-VEGF therapy for diabetic eye diseases. Asia Pac J Ophthalmol (Phila). 6:535–545. 2017.
36	Wu SL, Zhan DM, Xi SH and He XL: Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy. Int J Ophthalmol. 7:764–767. 2014.PubMed/NCBI
37	Wu S and He X: The correlation study of the expression of VEGF with t-PA and PAI expression in plasma and intraocular tissue in proliferative diabetic retinopathy. Zhonghua Yan Ke Za Zh. 50:448–453. 2014.In Chinese.
38	Zhang M, Chu S, Zeng F and Xu H: Bevacizumab modulates the process of fibrosis in vitro. Clin Exp Ophthalmol. 43:173–179. 2015. View Article : Google Scholar
39	Van Geest RJ, Lesnik-Oberstein SY, Tan HS, Mura M, Goldschmeding R, Van Noorden CJ, Klaassen I and Schlingemann RO: A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy. Br J Ophthalmol. 96:587–590. 2012. View Article : Google Scholar : PubMed/NCBI
40	Kuiper EJ, Van Nieuwenhoven FA, de Smet MD, van Meurs JC, Tanck MW, Oliver N, Klaassen I, Van Noorden CJ, Goldschmeding R and Schlingemann RO: The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy. PLoS One. 3:e26752008. View Article : Google Scholar : PubMed/NCBI
41	Zhang Q, Qi Y, Chen L, Shi X, Bai Y, Huang L, Yu W, Jiang Y, Zhao M and Li X: The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: Clinical and laboratory evidence. Br J Ophthalmol. 100:1443–1450. 2016. View Article : Google Scholar : PubMed/NCBI
42	Hu B, Zhang Y, Zeng Q, Han Q, Zhang L, Liu M and Li X: Intravitreal injection of ranibizumab and CTGF shRNA improves retinal gene expression and microvessel ultrastructure in a rodent model of diabetes. Int J Mol Sci. 15:1606–1624. 2014. View Article : Google Scholar : PubMed/NCBI
43	Cheung N, Mitchell P and Wong TY: Diabetic retinopathy. Lancet. 376:124–136. 2010. View Article : Google Scholar : PubMed/NCBI
44	Regmi S, Pathak S, Kim JO, Yong CS and Jeong JH: Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives. Eur J Cell Biol. 98:1510412019. View Article : Google Scholar : PubMed/NCBI
45	Navarro-Gonzalez JF and Mora-Fernandez C: The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 19:433–442. 2008. View Article : Google Scholar : PubMed/NCBI
46	Petersen AM and Pedersen BK: The anti-inflammatory effect of exercise. J Appl Physiol (1985). 98:1154–1162. 2005. View Article : Google Scholar