Abstract
Diabetes is a worldwide leading cause of mortality and morbidity, and type 1 diabetes (T1D) is the most common chronic autoimmune disorder in children and young adults. There is currently no definitive treatment for T1D. Stem cell administration appeared as an experimental treatment showing an improvement in the clinical outcome and restoration of tissue architecture in many disorders. Mesenchymal stem cells (MSCs) showed their capacity to generate insulin-producing cells as a promising potential treatment for diabetic patients. The present work aimed to study the effect of MSCs on the ultrastructure and laboratory findings of streptozotocin (STZ)-induced T1D in rats. Sixty male albino rats were divided into three groups: group I (control), group II (STZ-induced diabetic), and group III (STZ-induced diabetic-treated with MSCs). Ultrastructure study, as well as glucose and insulin measurements, was done for the three groups. The diabetic group showed significantly higher glucose and lower insulin levels compared to the other two groups, while the diabetic group treated with MSCs showed a non-significant difference compared to the control group. On the ultrastructure level, the diabetic group showed nuclear degeneration, loss of cytoplasmic organelles, loss of cell membranes, pyknotic nuclei, and apoptosis. All these findings were mostly reversed by the use of MSCs in the diabetic-treated group. We conclude that the use of MSCs reversed the laboratory and ultrastructure effect of STZ-induced T1D in rats.
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References
Abuarqoub D, Adwan S, Zaza R, Wehaibi S, Aslam N, Jafar H, Qinnah N, Awidi A (2023) Effective generation of functional pancreatic β cells from human-derived dental stem cells of apical papilla and bone-marrow-derived stem cells: a comparative study. Pharmaceuticals (Basel) 16(5):649
Akil AA, Yassin E, Al-Maraghi A, Aliyev E, Al-Malki K, Khalid A, Fakhro KA (2021) Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era. J Transl Med 19(1):137
Barbu E, Popescu MR, Popescu AC, Balanescu SM (2022) Inflammation as a precursor of atherothrombosis, diabetes and early vascular aging. Int J Mol Sci 23(2):963
Bohacova P, Holan V (2018) Mesenchymal stem cells and type 1 diabetes treatment. Vnitr Lek 64(7–8):725–728
Brown C, McKee C, Bakshi S, Walker K, Hakman E, Halassy S, Svinarich D, Dodds R, Govind CK, Chaudhry GR (2019) Mesenchymal stem cells: cell therapy and regeneration potential. J Tissue Eng Regen Med 13(9):1738–1755
Chen S, Du K, Zou C (2020) Current progress in stem cell therapy for type 1 diabetes mellitus. Stem Cell Res Ther 11(1):275
Cole JB, Florez JC (2020) Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol 16(7):377–390
Costes S, Bertrand G, Ravier MA (2021) Mechanisms of beta-cell apoptosis in type 2 diabetes-prone situations and potential protection by GLP-1-based therapies. Int J Mol Sci 22(10):5303
Dawson B, Trapp RG (2004) Methods of evidence-based medicine and decision analysis. Basic and Clinical Biostatistics, vol 12, 4th edn. Lange Medical Books, McGraw-Hill Professional, pp 231–257
DiMeglio LA, Evans-Molina C, Oram RA (2018) Type 1 diabetes. Lancet 391:2449–2462
Gabr MM, Sobh MM, Zakaria MM, Refaie AF, Ghoneim MA (2008) Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. Exp Clin Transplant Exp Clin Transplant 6(3):236–243
Gorabi AMA, Farhad S, Mona J, Kazempor, (2016) Mesenchymal Stem Cells (MSC) Effect in streptozotocin (STZ) induced type I diabetic rats. The Caspian Sea Journal 1:91–95
He Q, Wang L, Zhao R, Yan F, Sha S, Cui C, Song J, Hu H, Guo X, Yang M, Cui Y, Sun Y, Sun Z, Liu F, Dong M, Hou X, Chen L (2020) Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy. Stem Cell Res Ther 11(1):223
Hogrebe NJ, Ishahak M, Millman JR (2023) Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell 30(5):530–548
Ilonen J, Lempainen J, Veijola R (2019) The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol 15(11):635–650
Itkin-Ansari P, Demeterco C, Bossie S, de la Tour DD, Beattie GM, Movassat J, Mally MI, Hayek A, Levine F (2000) PDX-1 and cell-cell contact act in synergy to promote d-cell development in a human pancreatic endocrine precursor cell line. Mol Endocrinol 14(6):814–822
Laurent F, Hindelang C, Strosser MT, Mialhe P (1988) The ultrastructure of A, B and D pancreatic cells in normal and in diabetic ducks. Biol Struct Morphog 1(1):34–42
Li WY, Zhu GY, Yue WJ, Sun GD, Zhu XF, Wang Y (2019) KLF7 overexpression in bone marrow stromal stem cells graft transplantation promotes sciatic nerve regeneration. J Neural Eng 16(5):056011
Masini M, Martino L, Marselli L, Bugliani M, Boggi U, Filipponi F, Marchetti P, De Tata V (2017) Ultrastructural alterations of pancreatic beta cells in human diabetes mellitus. Diabetes Metab Res Rev 33(6):2894
Moreira A, Kahlenberg S, Hornsby P (2017) Therapeutic potential of mesenchymal stem cells for diabetes. J Mol Endocrinol 59(3):109–120
Morsy MHE, Nabil ZI, Darwish ST, Al-Eisa RA, Mehana AE (2023) Anti-diabetic and anti-adipogenic effect of harmine in high-fat-diet-induced diabetes in mice. Life (Basel) 13(8):1693
Ogle GD, James S, Dabelea D, Pihoker C, Svennson J, Maniam J, Klatman EL, Patterson CC (2022) Global estimates of incidence of type 1 diabetes in children and adolescents: results from the international diabetes federation atlas, 10th edition. Diabetes Res Clin Pract 183:109083. https://doi.org/10.1016/j.diabres.2021.109083
Oh JE, Choi OK, Park HS, Jung HS, Ryu SJ, Lee YD, Lee SA, Chung SS, Choi EY, Lee DS, Gho YS, Lee H, Park KS (2019) Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic beta-cell-derived components. Sci Rep 9(1):5343
Perkins BA, Sherr JL, Mathieu C (2021) Type 1 diabetes glycemic management: Insulin therapy, glucose monitoring, and automation. Science 373:522–527
Saliu TP, Kumrungsee T, Miyata K, Tominaga H, Yazawa N, Hashimoto K, Kamesawa M, Yanaka N (2022) Comparative study on molecular mechanism of diabetic myopathy in two different types of streptozotocin-induced diabetic models. Life Sci 1(288):120183
Sayed HM, Awaad AS, Abdel Rahman FES, Al-Dossari M, Abd El-Gawaad NS, Ahmed OM (2022) Combinatory effect and modes of action of chrysin and bone marrow-derived mesenchymal stem cells on streptozotocin/nicotinamide-induced diabetic rats. Pharmaceuticals (basel) 16(1):34. https://doi.org/10.3390/ph16010034
Shalaby RH, Rashed LA, Ismaail AE, Madkour NK, Elwakeel SH (2014) Hematopoietic stem cells derived from human umbilical cord ameliorate cisplatin-induced acute renal failure in rats. Am J Stem Cells 3(2):83–96
Smolinska V, Bohac M, Danisovic L (2023) Current status of the applications of conditioned media derived from mesenchymal stem cells for regenerative medicine. Physiol Res 72(S3):S233-S245
Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin induced diabetic mice. Diabetes 49(2):157–162
Tang D, Cao L, Burkhardt BR, Xia C, Litherland SA, Atkinson MA, Yang L (2004) In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53(7):1721–1732
Wang R, Zhao RC (2013) Mesenchymal stem cells for diabetes and related complications. In: Zhao RC (ed) Essentials of mesenchymal stem cell biology and its clinical translation. Springer Dordrecht Heidelberg New York London. Springer Science & Business Media, pp. 207–28
Weiss ML, Rao MS, Deans R, Czermak P (2016) Manufacturing cells for clinical use. Stem Cells International 1750697. Available from: Hindawi. published June. https://www.hindawi.com/journals/sci/2016/1750697/. Accessed Dec 2023
Wu M, Meng Q (2021) Current understanding of mesenchymal stem cells in liver diseases. World J Stem Cells 13(9):1349–1359
Yang L, Saudi LM, J, (2021) Influence of myrcene on inflammation, matrix accumulation in the kidney tissues of streptozotocin-induced diabetic rat. Biol Sci 28(10):5555–5560
Zhao Y, Cao Q, He Y, Xue Q, Xie L, Yan Y (2017) Impairment of endoplasmic reticulum is involved in β-cell dysfunction induced by microcystin-LR. Environ Pollut 223:587–594
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AFA and AK contributed to the study conception and design. All authors shared the development, material preparation, and data collection. The principle of the article and the first draft of the manuscript were written by Ashraf Kotb, which was also responsible for the laboratory effect analysis; AA and RE managed the processing and interpretation of the ultrastructure effect. All authors performed the literature search, revised, and commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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AlDomairy, A.F., kotb, A. & Elsabban, R.M. Ultrastructure and laboratory effect of mesenchymal stem cells in streptozotocin-induced type I diabetic rats. Comp Clin Pathol 33, 303–308 (2024). https://doi.org/10.1007/s00580-024-03551-z
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DOI: https://doi.org/10.1007/s00580-024-03551-z