دورية أكاديمية
Long-term effects of muscle-derived stem cell therapy on the regeneration of the urethra of female rats.
العنوان: | Long-term effects of muscle-derived stem cell therapy on the regeneration of the urethra of female rats. |
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المؤلفون: | Bilhar APM; Department of Gynecology, Universidade Federal de São Paulo, São Paulo, Brazil.; Department of Gynecology, Maternidade Escola Assis Chateaubriand, Universidade Federal do Ceará, Fortaleza, Brazil., Bortolini MAT; Department of Gynecology, Universidade Federal de São Paulo, São Paulo, Brazil. maria.augusta@gmail.com., Sé AB; Department of Gynecology, Universidade Federal de São Paulo, São Paulo, Brazil., Feitosa SM; Department of Gynecology, Universidade Federal de São Paulo, São Paulo, Brazil., Zanoteli E; Department of Neurology, Universidade de São Paulo, São Paulo, Brazil., Castro RA; Department of Gynecology, Universidade Federal de São Paulo, São Paulo, Brazil. |
المصدر: | International urogynecology journal [Int Urogynecol J] 2022 Apr; Vol. 33 (4), pp. 965-975. Date of Electronic Publication: 2021 Mar 03. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Country of Publication: England NLM ID: 101567041 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1433-3023 (Electronic) Linking ISSN: 09373462 NLM ISO Abbreviation: Int Urogynecol J Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Springer |
مواضيع طبية MeSH: | Nerve Growth Factor*/genetics , Nerve Growth Factor*/metabolism , Urethra*/injuries, Animals ; Desmin/metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Male ; Muscle, Skeletal ; RNA, Messenger/metabolism ; Rats ; Regeneration ; Stem Cell Transplantation |
مستخلص: | Introduction and Hypothesis: The aim was to analyze the long-term effects of muscle-derived stem cells (MDSCs) therapy in traumatized urethras of female rats regarding messenger ribonucleic acid (mRNA) expression of collagens 1 and 3, Ngf and Ki67; and the mRNA and protein expression of Myh11 and Myh2. Methods: Muscle-derived stem cells were injected into the tail vein of rats 3 days after trauma by vaginal distention. Urethras were analyzed from 30 animals divided into three groups: control without injury or treatment, trauma (30 days post-injury), and MDSC (30 days post-injury who received MDSC therapy). Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed. The Kruskal-Wallis and ANOVA tests were used with p < 0.05 indicating significance. Results: We detected increased Myh11 and Myh2 mRNA expression in the trauma group compared with the control group (p = 0.03 and p = 0.04 respectively). Ki67 and Col1a1 genes were overexpressed in the MDSC group compared with both the trauma (p = 0.02 and p = 0.008 respectively) and the control group (p = 0.01 and p = 0.03 respectively). Col3a1 gene was upregulated in the MDSC compared with the control group (p = 0.03). Ngf mRNA level was lower in the MDSC group than in the trauma group (p = 0.002). Myh11, Myh2, and Desmin proteins were overexpressed in the MDSC compared with the trauma group (1.5-fold, p = 0.01; 1.5-fold, p = 0.04; 1.3-fold, p = 0.01 respectively). Conclusions: Muscle-derived stem cell therapy may have had long-term structural and molecular effects on the injured urethra of female rats, particularly on markers of cell proliferation, neural growth factor, extracellular matrix, and muscle content. This study suggests that MDSC therapy acted mainly to produce urethral sphincter regeneration marked by increased immunohistochemical expression of the proteins desmin, smooth muscle Myh11, and skeletal muscle Myh2. (© 2021. The International Urogynecological Association.) |
References: | Abrams P, Cardozo L, Wagg A, Wein A. Pathophysiology of urinary incontinence, faecal incontinence and pelvic organ prolapse. 6th International Consultation on Incontinence, Tokyo; 2017. Huang J, Cheng M, Ding Y, et al. Modified vaginal dilation rat model for postpartum stress urinary incontinence. J Obstet Gynaecol Res. 2013;39(1):256–63. (PMID: 10.1111/j.1447-0756.2012.01959.x) Bortolini MAT, Feitosa SM, Bilhar PM, Salerno GR, Zanoteli E, Simões MJ, et al. Molecular and histomorphological evaluation of female rats urethral tissues after an innovative trauma model of prolonged vaginal distention: immediate, short-term and long-term effects. Int Urogynecol J. 2018;30(3):465–76. (PMID: 10.1007/s00192-018-3634-2) Chancellor MB, Yokoyama T, Tirney S, Mattes CE, Ozawa H, Yoshimura N, et al. Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility. Neurourol Urodyn. 2000;19(3):279–87. (PMID: 10.1002/(SICI)1520-6777(2000)19:3<279::AID-NAU9>3.0.CO;2-M) Lee JY, Cannon TW, Pruchnic R, Fraser MO, Huard J, Chancellor MB. The effects of periurethral muscle-derived stem cell injection on leak point pressure in a rat model of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14:31–7. (PMID: 10.1007/s00192-002-1004-5) Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, Groat WC, et al. Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency. Urology. 2004;63:780–5. (PMID: 10.1016/j.urology.2003.10.035) Cannon TW, Lee JY, Somogyi G, et al. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra. Urology. 2003;62:958–63. (PMID: 10.1016/S0090-4295(03)00679-4) Eberli D, Aboushwareb T, Soker S, et al. Muscle precursor cells for the restoration of irreversibly damaged sphincter function. Cell Transplant. 2012;21:2089–98. (PMID: 10.3727/096368911X623835) Peters KM, Dmochowski RR, Carr LK, et al. Autologous muscle derived cells for treatment of stress urinary incontinence in women. J Urol. 2014;192:469–76. (PMID: 10.1016/j.juro.2014.02.047) Stangel-Wojcikiewicz K, Jarocha D, Piwowar M, et al. Autologous muscle-derived cells for the treatment of female stress urinary incontinence: a 2-year follow-up of a Polish investigation. Neurourol Urodyn. 2014;33:324–30. (PMID: 10.1002/nau.22404) Carr LK, Robert M, Kultgen PL, et al. Autologous muscle derived cell therapy for stress urinary incontinence: a prospective, dose ranging study. J Urol. 2013;189:595–601. (PMID: 10.1016/j.juro.2012.09.028) Gräs S, Klarskov N, Lose G. Intraurethral injection of autologous minced skeletal muscle: a simple surgical treatment for stress urinary incontinence. J Urol. 2014;192:850–5. (PMID: 10.1016/j.juro.2014.04.005) Bilhar AP, Bortolini MA, Sé AB, et al. Molecular and immunohistochemical analysis of the urethra of female rats after induced trauma and intravenous therapy with muscle derived stem cells. Neurourol Urodyn. 2018;37(7):2151–9. (PMID: 10.1002/nau.23567) Hofer MD, Cheng EY, Bury MI, et al. Analysis of primary urethral wound healing in the rat. Urology 2014;84(1):246.e1–7. (PMID: 10.1016/j.urology.2014.04.012) Gharaibeh B, Lu A, Tebbets J, Zheng B, Feduska J, Crisan M, et al. Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique. Nat Protoc. 2008;3(9):1501–9. (PMID: 10.1038/nprot.2008.142) Phillips JI, Davies I. The comparative morphology of the bladder and urethra in young and old female C57BL/Icrfat mice. Exp Gerontol. 1980;15:551–62. (PMID: 10.1016/0531-5565(80)90008-X) Aufderklamm S, Aicher WK, Amend B, Stenzlaufderklamm A. Stress urinary incontinence and regenerative medicine: is injecting functional cells into the urethra feasible based on current knowledge and future prospects? Curr Opin Urol. 2019;29:394–9. (PMID: 10.1097/MOU.0000000000000624) Cruz M, Dissaranan C, Cotleur A, Kiedrowski M, Penn M, Damaser M. Pelvic organ distribution of mesenchymal stem cells injected intravenously after simulated childbirth injury in female rats. Obstet Gynecol Int. 2012;2012:612946. (PMID: 10.1155/2012/612946) Pan HQ, Kerns JM, Lin DL, Liu S, Esparza N, Damaser MS. Increased duration of simulated childbirth injuries results in increased time to recovery. Am J Phys Regul Integr Comp Phys. 2007;292(4):R1738–44. Deng K, Lin DL, Hanzlicek B, Balog B, Penn MS, Kiedrowski MJ, et al. Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model. Am J Physiol Renal Physiol. 2015;308:F92–F100. (PMID: 10.1152/ajprenal.00510.2014) Dissaranan C, Cruz MA, Kiedrowski MJ, Balog BM, Gill BC, Penn MS, et al. Rat mesenchymal stem cell secretome promotes elastogenesis and facilitates recovery from simulated childbirth injury. Cell Transplant. 2014;23:1395–406. (PMID: 10.3727/096368913X670921) Sadeghi Z, Isariyawongse J, Kavran M, Izgi K, Marini G, Molter J, et al. Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution. Int Urogynecol J. 2016;27:291–300. (PMID: 10.1007/s00192-015-2831-5) Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–36. (PMID: 10.1038/nri2395) Beamish JA, He P, Kottke-Marchant K, Marchant RE. Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev. 2010;16:467–91. (PMID: 10.1089/ten.teb.2009.0630) Lin G, Wang G, Banie L, et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2010;12:88–95. (PMID: 10.3109/14653240903350265) Choi JY, Chun SY, Kim BS, Kim HT, Yoo ES, Shon YH, et al. Pre-clinical efficacy and safety evaluation of human amniotic fluid-derived stem cell injection in a mouse model of urinary incontinence. Yonsei Med J. 2015;56(3):648–57. (PMID: 10.3349/ymj.2015.56.3.648) Wagatsuma A. Endogenous expression of angiogenesis-related factors in response to muscle injury. Mol Cell Biochem. 2007;298:151–9. (PMID: 10.1007/s11010-006-9361-x) Lim JJ, Jang JB, Kim JY, Moon SH, Lee CN, Lee KJ. Human umbilical cord blood mononuclear cell transplantation in rats with intrinsic sphincter deficiency. J Korean Med Sci. 2010;25:663–70. (PMID: 10.3346/jkms.2010.25.5.663) Corcos J, Loutochin O, Campeau L, Eliopoulos N, Bouchentouf M, Blok B, et al. Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence. Neurourol Urodyn. 2011;30(3):447–55. (PMID: 10.1002/nau.20998) Birk DE, Fitch JM, Babiarz JP, Doane KJ, Linsenmayer TF. Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J Cell Sci. 1990;95:649–57. (PMID: 10.1242/jcs.95.4.649) Ochodnicky P, Cruz CD, Yoshimura N, Michel MC. Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target. Neurourol Urodyn. 2011;30(7):1227–41. (PMID: 10.1002/nau.21022) Apfel SC. Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? Int Rev Neurobiol. 2002;50:393–413. (PMID: 10.1016/S0074-7742(02)50083-0) Luo X, Yao RS, Song H, Jiang XF, Lan JF, Shuai HL, et al. Study on human umbilical cord mesenchymal stem cells transplantation in treatment of stress urinary incontinence in rats. Zhonghua Fu Chan Ke Za Zhi. 2013;48(8):579–83. |
معلومات مُعتمدة: | Nº 17/2008 Conselho Nacional de Desenvolvimento Científico e Tecnológico |
فهرسة مساهمة: | Keywords: Adult stem cell; Muscle-derived stem cell; Regenerative medicine; Urethra; Urinary incontinence |
المشرفين على المادة: | 0 (Desmin) 0 (Ki-67 Antigen) 0 (RNA, Messenger) 9061-61-4 (Nerve Growth Factor) |
تواريخ الأحداث: | Date Created: 20210303 Date Completed: 20220422 Latest Revision: 20220520 |
رمز التحديث: | 20221213 |
DOI: | 10.1007/s00192-021-04708-y |
PMID: | 33655365 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1433-3023 |
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DOI: | 10.1007/s00192-021-04708-y |