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Bone marrow mesenchymal stem cells therapy on bilateral pelvic nerve crush-induced voiding dysfunction in rats

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Abstract

Introduction and hypothesis

Neurogenic voiding dysfunction can be induced after radical pelvic surgery and severely affects patients’ quality of life. This study aims to investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on neurogenic voiding dysfunction in male rats and explore the underlying mechanisms.

Methods

Thirty 4-week-old male Sprague-Dawley rats were randomly divided into three groups: (1) sham-operated (sham, n = 10), (2) intrabladder wall injection of phosphate buffer solution (PBS) after bilateral pelvic nerve crush (BPNC+PBS, n = 10), and (3) intrabladder wall injection of BMSCs after bilateral pelvic nerve crush (BPNC+BMSCs, n = 10). Four weeks postoperatively, functional and morphological examinations were performed.

Results

Compared to the sham group, BPNC rats manifested significant augmentation in the frequency of non-voiding contractions and postvoid residual and bladder capacity, and they had decreases in intravesical pressure and voiding efficiency. However, they were markedly improved after BMSC injection. Masson’s trichrome staining showed that the ratio of collagen area in bladder wall tissue significantly increased in the BPNC+PBS group but was reduced following BMSC injection. BPNC increased the protein expression of TGF-β1, Smad2/3, and collagen I/III but decreased the expression of α-SMA. BMSC injection stimulated higher expression levels of α-SMA and lower expression levels of the other target proteins. The expression levels of vesicular acetylcholine transporters were reduced at 4 weeks post-BPNC, whereas injection of BMSCs boosted the expression quantity.

Conclusions

BMSC therapy suppressed detrusor fibrosis, improved intravesical pressure and voiding efficiency, and partially restored voiding function in male rats after BPNC.

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References

  1. Derks M, van der Velden J, Frijstein MM, Vermeer WM, Stiggelbout AM, Roovers JP, de Kroon CD, Ter Kuile MM, Kenter GG. Long-term pelvic floor function and quality of life after radical surgery for cervical cancer: a multicenter comparison between different techniques for radical hysterectomy with pelvic lymphadenectomy. Int J Gynecol Cancer. 2016;26(8):1538–43. https://doi.org/10.1097/igc.0000000000000776.

    Article  PubMed  Google Scholar 

  2. Avulova S, Zhao Z, Lee D, Huang LC, Koyama T, Hoffman KE, Conwill RM, Wu XC, Chen V, Cooperberg MR, Goodman M, Greenfield S, Hamilton AS, Hashibe M, Paddock LE, Stroup A, Resnick MJ, Penson DF, Barocas DA. The effect of nerve sparing status on sexual and urinary function: 3-year results from the CEASAR study. J Urol. 2018;199(5):1202–9. https://doi.org/10.1016/j.juro.2017.12.037.

    Article  PubMed  Google Scholar 

  3. Akasu T, Sugihara K, Moriya Y. Male urinary and sexual functions after mesorectal excision alone or in combination with extended lateral pelvic lymph node dissection for rectal cancer. Ann Surg Oncol. 2009;16(10):2779–86. https://doi.org/10.1245/s10434-009-0546-x.

    Article  PubMed  Google Scholar 

  4. Salehi-Pourmehr H, Rahbarghazi R, Mahmoudi J, Roshangar L, Chapple CR, Hajebrahimi S, Abolhasanpour N, Azghani MR. Intra-bladder wall transplantation of bone marrow mesenchymal stem cells improved urinary bladder dysfunction following spinal cord injury. Life Sci. 2019;221:20–8. https://doi.org/10.1016/j.lfs.2019.02.011.

    Article  CAS  PubMed  Google Scholar 

  5. Groenendijk IM, van den Hoek J, Blok BFM, Nijman RJM, Scheepe JR. Long-term results of continent catheterizable urinary channels in adults with non-neurogenic or neurogenic lower urinary tract dysfunction. Scand J Urol. 2019;53(2-3):145–50. https://doi.org/10.1080/21681805.2019.1596156.

    Article  PubMed  Google Scholar 

  6. Yu A, Campeau L. Bone marrow mesenchymal stem cell therapy for voiding dysfunction. Curr Urol Rep. 2015;16(7):49. https://doi.org/10.1007/s11934-015-0516-8.

    Article  PubMed  Google Scholar 

  7. Muthu S, Jeyaraman M, Gulati A, Arora A. Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: systematic review and meta-analysis. Cytotherapy. 2021;23(3):186–97. https://doi.org/10.1016/j.jcyt.2020.09.007.

    Article  PubMed  Google Scholar 

  8. Mangır N, Türkeri L. Stem cell therapies in post-prostatectomy erectile dysfunction: a critical review. Can J Urol. 2017;24(1):8609–19.

    PubMed  Google Scholar 

  9. You D, Jang MJ, Song G, Shin HC, Suh N, Kim YM, Ahn TY, Kim CS. Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial. Cytotherapy. 2021;23(10):931–8. https://doi.org/10.1016/j.jcyt.2021.06.001.

    Article  CAS  PubMed  Google Scholar 

  10. Oliveira JT, Mostacada K, de Lima S, Martinez AM. Bone marrow mesenchymal stem cell transplantation for improving nerve regeneration. Int Rev Neurobiol. 2013;108:59–77. https://doi.org/10.1016/b978-0-12-410499-0.00003-4.

    Article  CAS  PubMed  Google Scholar 

  11. Satti HS, Waheed A, Ahmed P, Ahmed K, Akram Z, Aziz T, Satti TM, Shahbaz N, Khan MA, Malik SA. Autologous mesenchymal stromal cell transplantation for spinal cord injury: a phase I pilot study. Cytotherapy. 2016;18(4):518–22. https://doi.org/10.1016/j.jcyt.2016.01.004.

    Article  PubMed  Google Scholar 

  12. Ge Q, Wang M, Lin Y, Xu C, Xiao J, Shen Z. Establishment of animal model manifested as bladder neurogenic changes generated by bilateral pelvic nerve injury in male rats. Int Urol Nephrol. 2021;53(3):421–9. https://doi.org/10.1007/s11255-020-02668-8.

    Article  CAS  PubMed  Google Scholar 

  13. Li X, Zhang Y, Qi G. Evaluation of isolation methods and culture conditions for rat bone marrow mesenchymal stem cells. Cytotechnology. 2013;65(3):323–34. https://doi.org/10.1007/s10616-012-9497-3.

    Article  CAS  PubMed  Google Scholar 

  14. Shen Z, Pang Z, Jia R, Wu X, Dong C, Gao W, Liu D, Li B. Erectile functional restoration with genital branch of genitofemoral nerve to cavernous nerve transfer after bilateral cavernous nerve resection in the rat. Urology. 2014;84(4):983.e981–8. https://doi.org/10.1016/j.urology.2014.04.061.

    Article  Google Scholar 

  15. Fu CL, Apelo CA, Torres B, Thai KH, Hsieh MH. Mouse bladder wall injection. J Vis Exp. 2011;53:e2523. https://doi.org/10.3791/2523.

    Article  Google Scholar 

  16. Sartori AM, Schwab ME, Kessler TM. Ultrasound: a valuable translational tool to measure Postvoid residual in awake rats? Eur Urol Focus. 2020;6(5):916–21. https://doi.org/10.1016/j.euf.2019.11.016.

    Article  PubMed  Google Scholar 

  17. Sekido N, Kida J, Mashimo H, Wakamatsu D, Okada H, Matsuya H. Promising effects of a novel EP2 and EP3 receptor dual agonist, ONO-8055, on neurogenic underactive bladder in a rat lumbar canal stenosis model. J Urol. 2016;196(2):609–16. https://doi.org/10.1016/j.juro.2016.02.064.

    Article  CAS  PubMed  Google Scholar 

  18. Takaoka EI, Kurobe M, Okada H, Takai S, Suzuki T, Shimizu N, Kwon J, Nishiyama H, Yoshimura N, Chermansky CJ. Effect of TRPV4 activation in a rat model of detrusor underactivity induced by bilateral pelvic nerve crush injury. Neurourol Urodyn. 2018;37(8):2527–34. https://doi.org/10.1002/nau.23790.

    Article  CAS  PubMed  Google Scholar 

  19. Hannan JL, Powers SA, Wang VM, Castiglione F, Hedlund P, Bivalacqua TJ. Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia. Int Urogynecol J. 2017;28(7):1049–56. https://doi.org/10.1007/s00192-016-3223-1.

    Article  PubMed  Google Scholar 

  20. Kim SJ, Lee DS, Bae WJ, Kim S, Hong SH, Lee JY, Hwang TK, Kim SW. Functional and molecular changes of the bladder in rats with crushing injury of nerve bundles from major pelvic ganglion to the bladder: role of RhoA/rho kinase pathway. Int J Mol Sci. 2013;14(9):17511–24. https://doi.org/10.3390/ijms140917511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dewulf K, Weyne E, Gevaert T, Deruyver Y, Voets T, Ridder D, Everaerts W, Albersen M. Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity. BJU Int. 2019;123(5a):E86–e96. https://doi.org/10.1111/bju.14649.

    Article  CAS  PubMed  Google Scholar 

  22. Castiglione F, Bergamini A, Bettiga A, Bivalacqua TJ, Benigni F, Strittmatter F, Gandaglia G, Rigatti P, Montorsi F, Hedlund P. Perioperative betamethasone treatment reduces signs of bladder dysfunction in a rat model for neurapraxia in female urogenital surgery. Eur Urol. 2012;62(6):1076–85. https://doi.org/10.1016/j.eururo.2012.04.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Furuta A, Yamamoto T, Igarashi T, Suzuki Y, Egawa S, Yoshimura N. Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity, and nociception in a chemically induced interstitial cystitis-like rat model. Int Urogynecol J. 2018;29(11):1615–22. https://doi.org/10.1007/s00192-018-3592-8.

    Article  PubMed  Google Scholar 

  24. Vladimirova IA, Philyppov IB, Sotkis GV, Kulieva EM, Shuba YY, Gulak KL, Skryma R, Prevarskaya N, Shuba YM. Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: contribution of neurotransmitter-degrading ectoenzymes. Eur J Pharmacol. 2019;860:172529. https://doi.org/10.1016/j.ejphar.2019.172529.

    Article  CAS  PubMed  Google Scholar 

  25. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004;109(12):1543–9. https://doi.org/10.1161/01.Cir.0000124062.31102.57.

    Article  CAS  PubMed  Google Scholar 

  26. Pan M, Wang X, Chen Y, Cao S, Wen J, Wu G, Li Y, Li L, Qian C, Qin Z, Li Z, Tan D, Fan Z, Wu W, Guo J. Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves. Exp Neurol. 2017;292:92–101. https://doi.org/10.1016/j.expneurol.2017.03.005.

    Article  CAS  PubMed  Google Scholar 

  27. Kim JH, Lee SR, Song YS, Lee HJ. Stem cell therapy in bladder dysfunction: where are we? And where do we have to go? Biomed Res Int. 2013;2013:930713. https://doi.org/10.1155/2013/930713.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lee HJ, An J, Doo SW, Kim JH, Choi SS, Lee SR, Park SW, Song YS, Kim SU. Improvement in spinal cord injury-induced bladder fibrosis using mesenchymal stem cell transplantation into the Bladder Wall. Cell Transplant. 2015;24(7):1253–63. https://doi.org/10.3727/096368914x682125.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was funded by a grant from Anhui Provincial Natural Science Foundation (grant number 1708085QH179).

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China

    Zhou Shen, Qingyu Ge, Deyun Shen, Kaiguo Xia & Jun Xiao

Authors
  1. Zhou Shen
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  2. Qingyu Ge
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  3. Deyun Shen
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  4. Kaiguo Xia
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Contributions

Zhou Shen: Project development, Data collection, Manuscript writing.

Qingyu Ge: Project design, Data analysis, Manuscript editing.

Deyun Shen: Material preparation, Data collection.

Kaiguo Xia: Data collection.

Jun Xiao: Data collection, Data analysis.

Corresponding author

Correspondence to Qingyu Ge.

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Supplementary Information

ESM 1

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Fig. S1

Identification of BMSCs using flow cytometry. The cultured cells highly expressed CD90 (a) and CD105 (b) but were negative for CD34 (c) and CD45 (d). (PNG 327 kb)

High-resolution image (TIF 2557 kb)

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Shen, Z., Ge, Q., Shen, D. et al. Bone marrow mesenchymal stem cells therapy on bilateral pelvic nerve crush-induced voiding dysfunction in rats. Int Urogynecol J 33, 2485–2492 (2022). https://doi.org/10.1007/s00192-022-05099-4

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  • DOI: https://doi.org/10.1007/s00192-022-05099-4

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