Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome
Salamah, L., Abd El-Aziz, G., Fouad, H., Abdallah, M. (2023). Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome. EKB Journal Management System, 1(1), 52-67. doi: 10.21608/ejctr.2023.198196.1006
Lamis Abdelghani Salamah; Ghada Mahmoud Abd El-Aziz; Hanan Hassan Fouad; Marwa Fathi Abdallah. "Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome". EKB Journal Management System, 1, 1, 2023, 52-67. doi: 10.21608/ejctr.2023.198196.1006
Salamah, L., Abd El-Aziz, G., Fouad, H., Abdallah, M. (2023). 'Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome', EKB Journal Management System, 1(1), pp. 52-67. doi: 10.21608/ejctr.2023.198196.1006
Salamah, L., Abd El-Aziz, G., Fouad, H., Abdallah, M. Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome. EKB Journal Management System, 2023; 1(1): 52-67. doi: 10.21608/ejctr.2023.198196.1006

Assessment of the potential therapeutic effects of Mesenchymal Stem Cells in an experimental model of Cardiorenal Syndrome

Egyptian Journal of Cell and Tissue Research
Volume 1, Issue 1, January 2023, Page 52-67  XML PDF (779.81 K)
Document Type: Original articles
DOI: 10.21608/ejctr.2023.198196.1006
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Authors
Lamis Abdelghani Salamah email 1; Ghada Mahmoud Abd El-Aziz1; Hanan Hassan Fouad2; Marwa Fathi Abdallah1
1Medical Biochemistry and Molecular Biology department, Faculty of Medicine, Beni-Suef University, Egypt
2Medical Biochemistry and, Molecular Biology department, Faculty of Medicine, Cairo University, Egypt
Abstract
The goal of this study is to evaluate the efficacy of bone marrow derived mesenchymal stem cells (BMMSCs) in the prevention of fibrosis following induction of CRS type 3 in rats, and in addition, to assess their effect on FGF23 and Klotho genes, renal functions, and histopathological features. A total of eighteen male albino rats were enrolled in this study divided equally into 3 groups; group I: healthy control, group II: CRS without treatment, group III: CRS treated with BM-MSCs. Rats were
used to generate Cardiac Hypertrophy (in vivo), by ligating their right renal artery, and group III was injected with stem cells after the insult. Serum levels of urea and creatinine were assessed, FGF23 and Klotho genes expression in cardiac and renal tissue by quantitative real time PCR were evaluated. Histopathological examination of tissues was performed. Results revealed that serum levels of urea and creatinine were elevated with significant increase in FGF23 and decrease in KLOTHO levels in diseased group compared to control and treated group. In treated group with BMMSCs, FGF23 was markedly inhibited, and KLOTHO level was upregulated with little
significant difference between treated group and normal control. In addition, there was decrease in urea and creatinine levels. Histopathological examination of treated group revealed improvement of induced fibrosis in renal and cardiac tissues compared to diseased group. The data suggests that
MSCs might have therapeutic effect on cardiorenal syndrome type 3.
Keywords
FGF23/Klotho; Mesenchymal Stem Cell; experimental model; cardio renal syndrome
References
  1. Friedenstein A.J., Chailakhjan R.K. & Lalykina K.S. (1970): The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell and Tissue Kinetics. 3:393–403.
  2. Chawla L.S., Bellomo R., Bihorac A., et al. (2017): Acute kidney disease and renal recovery: Consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat. Rev. Nephrol. 13:241– 257.
  3. Sávio-Silva C., Beyerstedt S., Soinski-Sousa P.E., et al. (2020): Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease: A Review of the Studies Using Syngeneic, Autologous, Allogeneic, and Xenogeneic Cells. Stem Cells Int. 2020:1–28.
  4. Cheng G.S., Wang X.Y., Li Y.X., et al. (2017): Let-7a-transfected mesenchymal stem cells ameliorate monocrotaline-induced pulmonary hypertension by suppressing pulmonary artery smooth muscle cell growth through STAT3-BMPR2 signaling. Stem Cell Res. Ther. 8: 11.
  5. Christov M., Waikar S.S., Pereira R.C., et al. (2013): Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int. 84: 639– 641.
  6. Da Cruz Junho C.V., Caio‐Silva W., Ruiz‐Hurtado G., et al. (2019): Characterization of Klotho/FGF23 signaling in cardiorenal syndrome‐ induced cardiac hypertrophy. The FASEB Journal. 33: 831.1-831.1.
  7. Raafat N., Abdel Aal S., Abdo F., et al. (2015): Mesenchymal stem cells, In vivo therapeutic application ameliorates carbon tetrachloride induced liver fibrosis in rats. The International Journal of Biochemistry and Cell Biology. 68: 109–118.
  8. Richter M., Lautze H.J., Walther T., et al. (2015): The failing heart is a major source of circulating FGF23 via oncostatin M receptor activation. J Heart Lung Transplant. 34:1211–1214.
  9. Christov M., Waikar S.S., Pereira R.C., et al. (2013): Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int. 84: 639– 641.
  10. Leifheit-Nestler M., Grabner A., Hermann L., et al. (2017): Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats. Nephrol Dial Transplant. 32:1493–1503.
  11. Mace M.L., Gravesen E., Nordholm A., et al. (2017): Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia. Kidney Int. 92:165-178.
  12. Leaf D.E., Siew E.D., Eisenga M.F., et al. (2018): Fibroblast growth factor 23 associates with death in critically ill patients. Clin J Am Soc Nephrol. 13:531-541.
  13. Shi M., McMillan K.L., Wu J., et al. (2018): Cisplatin nephrotoxicity as a model of chronic kidney disease. Lab Invest. 98:1105–1121.
  14. Hu M.C., Shi M., Zhang J., et al. (2010): Klotho deficiency is an early biomarker of renal ischemia–reperfusion injury and its replacement is protective. Kidney Int. 78: 1240–1251.
  15. Hu M.C., Kuro-O M. & Moe O.W. (2013): Klotho and Chronic Kidney Disease. Contrib. Nephrol. 180:47–63.
  16. Kim A.J., Ro H., Kim H., et al. (2016): Klotho and S100A8/A9 as discriminative markers between pre-renal and intrinsic acute kidney injury. PLoS One. 11:e0147255.
  17. Seo M.Y., Yang J., Lee J.Y., et al. (2015): Renal klotho expression in patients with acute kidney injury is associated with the severity of the injury. Korean J Intern Med. 30:489-495.
  18. Bian A., Neyra J.A., Zhan M., et al. (2015): Klotho, stem cells, and aging. Clin Interv Aging. 10:1233-43.
  19. Ni W., Fang Y., Xie L., et al. (2015): Adipose-Derived Mesenchymal Stem Cells Transplantation Alleviates Renal Injury in Streptozotocin- Induced Diabetic Nephropathy. J. Histochem. Cytochem. 63:842–853.
  20. Kieswich J.E., Chen J., Alliouachene S., et al. (2018): A novel model of reno-cardiac syndrome in the C57BL/ 6 mouse strain. BMC Nephrol. 19:346.
  21. Zhu F., Chong L.O., Pei G., et al. (2017): Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial cell dependent Sox9 activation. Oncotarget. 8:70707–70726.
  22. Rodrigues C.E., Capcha J.M., de Braganca A.C., et al. (2017): Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury. Stem Cell Res. Ther. 8:19.
  23. Florea V., Rieger A.C., DiFede D.L., et al. (2017): Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients with Ischemic Cardiomyopathy (The TRIDENT Study). Circ. Res. 121:1279–1290.
  24. Alatab S., Shekarchian S., Najafi I., et al. (2019): Systemic Infusion of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in Peritoneal Dialysis Patients: Feasibility and Safety. Cell J. 20:483–495.
  25. Saad A., Dietz A.B., Herrmann S.M.S., et al. (2017): Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease. J. Am. Soc. Nephrol. 28:2777–2785.
  26. Swaminathan M., Stafford-Smith M., Chertow G.M., et al. (2018): Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery. J. Am. Soc. Nephrol. 29:260–267.
  27. Makhlough A., Shekarchian S., Moghadasali R., et al. (2017): Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients. Stem Cell Res. Ther. 8:116.
  28. Lin W., Li H.Y., Yang Q., et al. (2021): Administration of mesenchymal stem cells in diabetic kidney disease: A systematic review and meta-analysis. Stem Cell Res. Ther. 12:1–21.
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