Role of Stem Cell Therapy in Diabetic Cardiomyopathy in Rats: Histological and Immunohistochemical study

Document Type : Original Article

Authors

1 Anatomy and Embryology department, Faculty of Medicine, Beni-Suef University, Egypt

2 Anatomy and Embryology department, Faculty of Medicine, Cairo University, Egypt

3 Histology department, Faculty of Medicine, Beni-Suef University, Egypt

Abstract

Background: Diabetes mellitus is one of the main causes of death due to the complications that involve many organs such as heart, kidney, retina and others. Mesenchymal stem cell (MSC) has been demonstrated to be effective in treatment of diabetes. Aim of the work: To evaluate the effect of stem cells in the treatment of diabetic cardiomyopathy clarifying their role in oxidative stress and inflammation. Material and methods: 30 adult male albino rats were equally divided into 3 groups: control group (group I): received 1ml saline by intra-peritoneal (IP) injection. Streptozotocin-treated group (group II): received Streptozotocin (STZ) (60mg/kg BW, I.P.) for induction of diabetes then were sacrificed after 4 weeks. Steptozotocin+ Stem cell-treated group (group III): received STZ for induction of diabetes and they were left for 4 weeks then they were injected once intravenously with 1 million units of MSC then were sacrificed after 4 weeks. The heart sections were examined Histologically with H&E and Masson’s Trichrome Stain and Immunohistochemically for endothelial Nitric Oxide Synthase (eNOS). A morphometric study and statistical analysis were performed. Results: DM caused inflammation, degeneration, fibrosis and decreased eNOS Immunoexpression of the cardiac muscle fibers. The administration of MSCs improved pathological changes and increased eNOS Immunoexpression in the heart. Conclusion: MSCs administration proved to have effective therapeutic role in treating diabetic cardiomyopathy

Keywords


  1. Peng BY, Dubey NK, Mishra VK, Tsai FC, Dubey R, Deng WP and Wei HJ : Addressing Stem Cell Therapeutic Approaches in Pathobiology of Diabetes and Its Complications.Journal of Diabetes Research, 2018; Article ID 7806435, 16P.
  2. Babiker NE, Gassoum A, Abdelraheem NE, Arbab MA, ALDeaf SA , El-Sheikh MA and Musa HH. The progress of stem cells in the treatment of diabetes mellitus type 1. Prog Stem Cell, 2017; 4(1): 175-188.
  3. Zang L, Hao H, Liu J, Li1 Y, Han W and Mu Y.Mesenchymal stem cell therapy in type 2 diabetes mellitus. DiabetolMetabSyndr, 2017; 9:36.
  4. Mousa F, Abdel-Aziz KK, Abdel Gawad H, Mahmoud SS and Elgamel MS. Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats. International Journal of Science and Research (IJSR), 2016; Volume 5 Issue 2, P: 1624-1631. 
  5. Graham ML, Janecek JL, Kittredge JA, Hering BJ and Schuurman HJ. The Streptozotocin-Induced Diabetic Nude Mouse Model: Differences between Animals from Different Sources: Comparative Medicine Copyright 2011 by the American Association for Laboratory Animal Science,2011; Vol 61, No 4 August 2011 P: 356–360
  6.   Berardis S., Sattwika D. and Sokal E. Use of mesenchymal stem cells to treat liver fibrosis. World J Gastroenterol, 2015; 3: 742–758.
  7.  Volarevic V, Nurkovic J, Arsenijevic N and Stojkovic M. Concise review: therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis. Stem Cells,2014; 32:2818–2823
  8. Srinivasan K, Viswanad B, Asrat L, Kaul CL and Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res,2005; 52: 313–332
  9. Ngoc, K ., van Phuc,P.,  Nhung, T .,Thuy, D . and Nguyet,M. Improving the efficacy of type 1 diabetes therapyby transplantation of immunoisolated insulin-producing cells.Human Cell, 2011; 24: 86–95.
  10.  Cesaretti ML, Ginoza M, Ribeiro AB and Kohlmann OJ.Systemic hemodynamic and left ventricular function of diabetic-induced hypertensive rats. Arq Bras EndocrinolMetabol, 2010; 54(9):842-851.
  11. Bluestone JA, Herold K and EisenbarthG.Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature,2010; 464:1293-1300.
  12. Ikebukuro K, Adachi Y, Yamada Y, Fujimoto S, Seino Y and Oyaizu H.Treatment of Streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone Marrow cells via portal vein in rats. Transplantation. 2002; 73(4): 512-518.
  13. Kajiyama H, Hamazaki TS, Tokuhara M, Masui SH, Okabayashi K, Ohnuma K, Yabe SH, Yasuda K, Ishiura SH, Okochi H and Asashima M. Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. Int. J. Dev. Biol, 2010; 54, 699–705.     
  14. Carr CA, Stuckey DJ and Tatton L. Bone marrow-derived stromal cells home to and remain in the infarcted rat heart but fail to improve function: an in vivo cine-MRI study. Am J Physiol Heart CircPhysiol,2008; 295(2):H533.
  15. Jiang TS, Cai L, Ji WY, Hui YN, Wang YS, Hu D and Zhu J. Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats. Mol Vis,2010; 16: 1304-1316.
  16. Liu  S.,  Zhao  C.,  Yang  C.,  Li  X.,  Huang  H.,  Liu  N.,  Li  S.,  Wang  X.  and  Liu  J. Gambogic  acid  suppresses  pressure  overload  cardiac  hypertrophy  in  rats. American  Journal of Cardiovascular Disease,2013; 3(4): 227–238
  17. Kiernan J.A. Staining with dyes in one or two colours. In Histological and Histochemical Methods:  Theory and Practice, 5thedition.  Scion Publishing Ltd.  Vantage Business Park, Bloxham Road, Banbury, UK. 2015; pp: 137-169.
  18.  Bancroft J.D. and Layton C. Connective and mesenchymal tissues with their stains. Theory and Practice of Histological Techniques. 7th` edition. Churchill Livingstone, Edinburgh, London, Madrid, Melbourne, New York and Tokyo, 2013; pp: 200-205.
  19.  Takahashi T and Harris RC. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy. Lessons from Diabetic eNOS Knockout Mice. Journal of Diabetes Research, Volume 2014;  Article ID 590541.17 pages.
  20. Emsley R, Dunn G and White IR. Mediation and moderation of  treatment effects in randomized controlled trails of complex interventions. Stat Methods Med Res, 2010; 19:237-270.
  21. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care, 2015; (38): 8-16 and (16): 43-56
  22. Othman AI, El-Sawi MR, El-Missiry MA and Abukhalil MH. Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats. Biomedicine &Pharmacotherapy,2017;  94, 362–373.
  23. Ji Y, Zhao Z, Cai T, Yang P and Cheng M. Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP-triggered apoptosis via the inhibition of the IRE-α pathway. Molecular medicine reports, 2014; 9: 1254-1258
  24. Hamza AA, Fikry EM, Abdallah W and Amin A. Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats. Scientific Reports, 2018; 8:9827.
  25. Liu M, Chen H, Jiang J, Zhang Z, Wang C, Zhang N, Dong L, Hu X, Zhu W, Yu H and Wang J. Stem cells and diabetic cardiomyopathy: from pathology to therapy. Heart Fail Rev, 2016; 21:723–736
  26. Glass CE, Singal PK and Singla DK. Stem cells in the diabetic infarcted heart. Heart Fail Rev, 2010;15(6): 581–588.
  27. Felaco M, Grilli A, De Lutiis MA, Patruno A, Libertini N, Taccardi AA, Napoli PD, Giulio CD, Barbacane R and Conti P.Endothelial Nitric Oxide Synthase (eNOS) Expression and Localization in Healthy and Diabetic Rat Hearts. Annals of Clinical & Laboratory Science, 2001; vol. 31, no. 2, P. 179-186.
  28. Xia R, Zhao B, Wu Y, Hou J, Zhang L, Xu J and Xia ZY. Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and AttenuatesMyocardial Ischemia/Reperfusion Injury in Diabetic Rats. Journal of Biomedicine and Biotechnology, 2011; Article ID 767930, 8 pages.
  29. Suvorava T, Nagy N, Pick S, Lieven O, Ruther U, Dao VT, Fischer JW, Weber M and Kojda G. Impact of eNOS-Dependent Oxidative Stress on Endothelial Function and Neointima Formation. Antioxidants & Redox signaling, 2015; Volume 23.p:711-723.
  30. Abdel Aziz MT, El-Asmar MF, Haidara M, Atta HM, Roshdy NK, Rashed LA, Sabry D, Youssef MA, Abdel Aziz AT and Moustafa M. Effect of bone marrow-derived mesenchymal stem cells on cardiovascular complications in diabetic rats: Med SciMonit, 2008; 14(11): BR 249-255.