Neonatal Bladder-derived Mesenchymal Stem Cells Ameliorate Bladder Dysfunction in Diabetic Rat Models
Vol. 17 No. 4 (2020),
24 June 2020
Purpose: To evaluate the effect of a new mesenchymal stem cell type derived from the neonatal bladder (nMSC-B) on diabetic bladder dysfunction (DBD).
Materials and Methods: nMSC-B were harvested from neonatal male Sprague-Dawley rat’s bladder and expanded in culture. nMSC-B were transferred to Type-1 diabetic rats which were induced by a single dose 45 mg/kg Streptozocin (STZ). Stem cells were transferred via intraperitoneally (IP) (DM-IP group, n:6) and by direct injection to the detrusor (DM-D group, n:6) at 12th week following diabetes and compared with Phosphate Buffered Saline (PBS) injected diabetic rats (DM-PBS group, n:6) and age-matched PBS injected non-diabetic normal rats (NR-PBS group, n:6). All rats were evaluated histopathologically and functionally four weeks after the stem cell treatment.
Results: nMSC-B showed improvement in both voiding function and bladder structure. The maximum voiding pressure (MVP) values in the DM-PBS group were lower compare to DM-IP, DM-D and NR-PBS groups (13.27 ± 0.78 vs 16.27 ± 0.61, 28.59 ± 2.09, 21.54 ± 1.00, respectively, P < .001). There was a significant improvement for MVP values in stem cell-treated groups. Immunohistochemical examination revealed decreased bladder smooth muscle (SM), increased fibrosis and desquamation in urothelia in diabetic groups compared to normal group(P < .001).
We detected recovery in the stem cell groups. This recovery was more evident in DM-D group. No statistical difference was observed in SM and fibrosis between DM-D and NR-PBS groups (P = .9).
Conclusion: It was shown that nMSCBs provided amelioration of DBD. We think that nMSC-B constitutes an effective treatment method in DBD.
Control CfD, Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention. 2011;201.
Frimodt-Møller C. Diabetic cystopathy: epidemiology and related disorders. Ann Intern Med. 1980 Feb;92(2 Pt 2):318-21
Daneshgari F, Liu G, Birder L, Hanna-Mitchell AT, Chacko S. Diabetic bladder dysfunction: current translational knowledge. J Urol. 2009;182 (6 Suppl):S18-26.
Andersson Colaco M, Osman NI, Karakeçi A, Artibani W, Andersson KE, Badlani GH. Current concepts of the acontractile bladder. BJU Int. 2018 Aug;122(2):195-202. doi: 10.1111/bju.14236. Epub 2018 May 3. Review.
Chai T. C. Kudze T. New therapeutic directions to treat underactive bladder. Investigative and clinical urology, 2017; 58(Suppl 2), S99-S106.
Gotherstrom C, West A, Liden J, Uzunel M, Lahesmaa R, Le Blanc K. Difference in gene expression between human fetal liver and adult bone marrow mesenchymal stem cells. Haematologica. 2005;90 (8):1017-26.
Bobis S, Jarocha D, Majka M. Mesenchymal stem cells: characteristics and clinical applications. Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society. 2006;44 (4):215-30.
Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009;217 (2):318-24.
Daneshgari F, Liu G, Imrey PB. Time dependent changes in diabetic cystopathy in rats a include compensated and decompensated bladder function. J Urol. 2006;176 (1):380-6.
Fu CL, Apelo CA, Torres B, Thai KH, Hsieh MH. Mouse bladder wall injection. Journal of visualized experiments: JoVE. 2011 (53):e2523
Underwood, W., Anthony, R., Cartner, S., Corey, D., Grandin, T., Greenacre, C. B., & Miller, D. AVMA guidelines for the euthanasia of animals: 2013 Edition. Schaumburg, IL: American Veterinary Medical Association
Magavi, S. S., & Macklis, J. D. Identification of newborn cells by BrdU labeling and immunocytochemistry in vivo. In Neural Stem Cells. 2008, pp. 335-343. Humana Press.
Tu DD, Seth A, Gil ES, Kaplan DL, Mauney JR, Estrada CR, Jr. Evaluation of biomaterials for bladder augmentation using cystometric analyses in various rodent models. Journal of visualized experiments: JoVE. 2012
Kim, J. H., Lee, H. J., & Song, Y. S. (2014). Treatment of bladder dysfunction using stem cell or tissue engineering technique. Korean journal of urology, 55(4), 228-238
Dong X, Zhang T, Liu Q, Zhu J, Zhao J, Li J, Sun B, Ding G, Hu X, Yang Z, Yuanyuan Zhang, Longkun Li, M.D., Ph.D. Beneficial effects of urine-derived stem cells on fibrosis and apoptosis of myocardial, glomerular and bladder cells. Mol Cell Endocrinol. 2016 May 15;427:21-32. doi: 10.1016/j.mce.2016.03.001. Epub 2016 Mar 4.
Liang, C. C., Shaw, S. W. S., Huang, Y. H., Lin, Y. H., Lee, T. H. . Improvement in bladder dysfunction after bladder transplantation of amniotic fluid stem cells in diabetic rats. Scientific reports, 2018; 8(1), 2105.
David C Hess &Cesar V Borlongan “Cell-based therapy in ischemic stroke” Journal Volume 8, 2008 - Issue 8 Pages 1193-1201
Andersson K-E. Potential of stem cell treatment in detrusor dysfunction. Adv Drug Deliv Rev 2015;82–83:117–22. doi:10.1016/j.addr.2014.10.017.
Lu SH, Cannon TW, Chermanski C, Pruchnic R, Somogyi G, Sacks M, de Groat WC, Huard J, Chancellor MB (2003) Musclederived stem cells seeded into acellular scaffolds develop calcium- dependent contractile activity that is modulated by nicotinic receptors. Urology 61(6):1285–1291
Zhang, H., Qiu, X., Shindel, A. W., Ning, H., Ferretti, L., Jin, X., ... & Lue, T. F. (2011). Adipose tissue-derived stem cells ameliorate diabetic bladder dysfunction in a type II diabetic rat model. Stem cells and development, 21(9), 1391-1400
Liu J, Huang J, Lin T, Zhang C, Yin X. Cell-to-cell contact induces human adipose tissue-derived stromal cells to differentiate into urothelium-like cells in vitro. Biochemical and biophysical research communications. 2009;390 (3):931-6
Caplan AI. Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9:11–15. Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012;10:709–716.
Lockhart S. T, Turrigiano, G. G., & Birren, S. J. (1997). Nerve growth factor modulates synaptic transmission between sympathetic neurons and cardiac myocytes. Journal of Neuroscience, 17(24), 9573-9582
Liu G, Li M, Vasanji A, Daneshgari F. Temporal diabetes and diurezis-induced alteration of nerves and vasculature of the urinary bladder in the rat. BJU international. 2011;107 (12):1988-93.
Beshay E, Carrier S. Oxidative stress plays a role in diabetes-induced bladder dysfunction in a rat model. Urology. 2004;64 (5):1062-7.
Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 2007;9:204
Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Experimental biology and medicine. 2001;226 (6):507-20.
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418:41-9.
Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Cell death and differentiation. 2014;21 (2):216-25
Weiner LP. Definitions and criteria for stem cells. Methods in molecular biology. 2008;438:3-8
- Abstract Viewed: 0 times
- pdf/5504 Downloaded: 0 times