Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
권호 표지
DOI QR코드

DOI QR Code

Transplantation of human adipose-derived stem cells into the urethra ameliorates stress urinary incontinence and blunts the induction of c-Fos immunoreactivities in brain areas related to micturition in female rats

  • Kim, Sung-Eun (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Ko, Il-Gyu (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Kim, Bo-Kyun (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Sung, Yun-Hee (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Shin, Mal-Soon (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Cho, Se-Hyung (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Kim, Chang-Ju (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Kim, Khae-Hawn (Department of Urology, Gil Medical Center, Gachon University of Medicine and Science) ;
  • Lee, Kyo-Won (Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kim, Dong-Hee (Department of Ophthalmology, College of Medicine, Chungju Hospital, Konkuk University)
  • Received : 2010.08.09
  • Accepted : 2010.08.16
  • Published : 2010.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Stress urinary incontinence (SUI) is a common condition that primarily affects women. Here, we investigate the effects of human adipose-derived stem cells (ADSCs) in a rodent model of SUI. Female Sprague-Dawley rats at 7 weeks of age were randomly divided into three groups (n=8 per group): sham-operation, SUI-induction by transabdominal urethrolysis, and SUI-induction followed by transplantation of human ADSCs into the urethra. The abdominal leak point pressure at 8 weeks after the operation was markedly decreased by transabdominal urethrolysis, confirming successful induction of SUI. Interestingly, transplantation of human ADSCs into the urethra significantly blunted the decrease of abdominal leak point pressure in SUI-induced rats. Accordingly, we observed expression of ${\alpha}$-smooth muscle actin in a significant proportion of transplanted ADSCs, indicating differentiation of ADSCs into smooth muscle cells in the urethra. Moreover, the SUI-induced elevations of c-Fos immunoreactivities in the pontine micturition center (PMC) and in the ventrolateral periaqueductal gray (vlPAG) were clearly suppressed by transplantation of human ADSCs. These results imply that human ADSCs can be an effective therapeutic modality to ameliorate the symptoms of SUI.

Keywords

References

  1. Athwal BS, Berkley KJ, Hussain I, Brennan A, Craggs M, Sakakibara R, Frackowiak RS, Fowler CJ. 2001. Brain responses to changes in bladder volume and urge to void in healthy men. Brain. 124:369-377. https://doi.org/10.1093/brain/124.2.369
  2. Balmforth J, Cardozo LD. 2003. Trends toward less invasive treatment of female stress urinary incontinence. Urology. 62:52-60. https://doi.org/10.1016/S0090-4295(03)00677-0
  3. Behbehani MM. 1995. Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol. 46:575-605. https://doi.org/10.1016/0301-0082(95)00009-K
  4. Blok BF, Holstege G. 1997. Ultrastructural evidence for a direct pathway from the pontine micturition center to the parasympathetic preganglionic motoneurons of the bladder of the cat. Neurosci Lett. 222:195-198. https://doi.org/10.1016/S0304-3940(97)13384-5
  5. Cho JA, Park H, Kim HK, Lim EH, Seo SW, Choi JS, Lee KW. 2009. Hyperthemia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line. Cancer. 115:311-323. https://doi.org/10.1002/cncr.24032
  6. Chung IM, Kim YS, Sung YH, Kim SE, Ko IG, Shin MS, Park HJ, Ham DH, Lee HJ, Kim KJ, et al. 2008. Effects of acupuncture on abdominal leak point pressure and c-Fos expression in the brain of rats with stress urinary incontinence. Neurosci Lett. 439:18-23. https://doi.org/10.1016/j.neulet.2008.04.100
  7. Fu Q, Song XF, Liao GL, Deng CL, Cui L. 2010. Myoblasts differentiated from adipose-derived stem cells to treat stress urinary incontinence. Urology. 75:718-723. https://doi.org/10.1016/j.urology.2009.10.003
  8. Furuta A, Carr LK, Yoshimura N, Chancellor MB. 2007. Advances in the understanding of stress urinary incontinence and the promise of stem-cell therapy. Rev Urol. 9:106-112.
  9. Guzowski JF, Timlin JA, Roysam B, McNaughton BL, Worley PF, Barnes CA. 2005. Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr Opin Neurobiol. 15:599-606. https://doi.org/10.1016/j.conb.2005.08.018
  10. Hsieh GC, Klutke JJ, Kobak WH. 2001. Low valsalva leakpoint pressure and success of retropubic urethropexy. Int Urogynecol J Pelvic Floor Dysfunct. 12:46-50. https://doi.org/10.1007/s001920170094
  11. Jack GS, Almeida FG, Zhang R, Alfonso ZC, Zuk PA, Rodriguez LV. 2005. Processed lipoaspirate cells for tissue engineering of the lower urinary tract: implications for the treatment of stress urinary incontinence and bladder reconstruction. J Urol. 174:2041-2045. https://doi.org/10.1097/01.ju.0000176489.96993.84
  12. Kavia RB, Dasgupta R, Fowler CJ. 2005. Functional imaging and the central control of the bladder. J Comp Neurol. 493:27-32. https://doi.org/10.1002/cne.20753
  13. Kerns JM, Damaser MS, Kane JM, Sakamoto K, Benson JT, Shott S, Brubaker L. 2000. Effects of pudendal nerve injury in the female rat. Neurourol Urodyn. 19:53-69. https://doi.org/10.1002/(SICI)1520-6777(2000)19:1<53::AID-NAU7>3.0.CO;2-8
  14. Kwon D, Kim Y, Pruchnic R, Jankowski R, Usiene I, de Miguel F, Huard J, Chancellor MB. 2006. Periurethral cellular injection: comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence. Urology. 68:449-454. https://doi.org/10.1016/j.urology.2006.03.040
  15. Lee JY, Cannon TW, Pruchnic R, Fraser MO, Huard J, Chancellor MB. 2003. The effects of periurethral musclederived stem cell injection on leak point pressure in a rat model of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 14:31-37. https://doi.org/10.1007/s00192-002-1004-5
  16. Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, Lue TF, Lin CS. 2010. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 12:88-95. https://doi.org/10.3109/14653240903350265
  17. Lin HK, Cowan R, Moore P, Zhang Y, Yang Q, Peterson JA Jr, Tomasek JJ, Kropp BP, Cheng EY. 2004. Characterization of neuropathic bladder smooth muscle cells in culture. J Urol. 171:1348-1352. https://doi.org/10.1097/01.ju.0000108800.47594.8b
  18. Mallory BS, Roppolo JR, de Groat WC. 1991. Pharmacological modulation of the pontine micturition center. Brain Res. 546:310-320. https://doi.org/10.1016/0006-8993(91)91495-M
  19. Miller KL. 2005. Stress urinary incontinence in women: review and update on neurological control. J Womens Health. 14:595-608. https://doi.org/10.1089/jwh.2005.14.595
  20. Mitsui T, Kakizaki H, Matsuura S, Tanaka H, Yoshioka M, Koyanagi T. 2003. Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat. Brain Res. 967:81-88. https://doi.org/10.1016/S0006-8993(02)04226-9
  21. Morgan JI, Curran T. 1991. Proto-oncogene transcription factors and epilepsy. Trends Pharmacol Sci. 12:343-349. https://doi.org/10.1016/0165-6147(91)90594-I
  22. Nour S, Svarer C, Kristensen JK, Paulson OB, Law I. 2000. Cerebral activation during micturition in normal men. Brain. 123:781-789. https://doi.org/10.1093/brain/123.4.781
  23. Phull H, Salkini M, Escobar C, Purves T, Comiter CV. 2007. The role of angiotensin II in stress urinary incontinence: A rat model. Neurourol Urodyn. 26:81-88. https://doi.org/10.1002/nau.20339
  24. Radley SC, Chapple CR, Bryan NP, Clarke DE, Craig DA. 2001. Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study. Neurourol Urodyn. 20:43-52. https://doi.org/10.1002/1520-6777(2001)20:1<43::AID-NAU6>3.0.CO;2-F
  25. Rodella L, Rezzani R, Gioia M, Tredici G, Bianchi R. 1998. Expression of Fos immunoreactivity in the rat supraspinal regions following noxious visceral stimulation. Brain Res Bull. 47:357-366. https://doi.org/10.1016/S0361-9230(98)00123-3
  26. Rodriguez LV, Alfonso Z, Zhang R, Leung J, Wu B, Ignarro LJ. 2006. Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc Natl Acad Sci USA. 103:12167-12172. https://doi.org/10.1073/pnas.0604850103
  27. Rodriguez LV, Chen S, Jack GS, de Almeida F, Lee KW, Zhang R. 2005. New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. Am J Physiol Regul Integr Comp Physiol. 288:R1332-R1338. https://doi.org/10.1152/ajpregu.00760.2004
  28. Sievert KD, Emre Bakircioglu M, Tsai T, Dahms SE, Nunes L, Lue TF. 2001. The effect of simulated birth trauma and/or ovariectomy on rodent continence mechanism. Part I: functional and structural change. J Urol. 166:311-317. https://doi.org/10.1016/S0022-5347(05)66151-4
  29. Sim YJ, Kim H, Shin MS, Chang HK, Shin MC, Ko IG, Kim KJ, Kim TS, Kim BK, Rhim YT, et al. 2008. Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcoholintoxicated mothers. Brain Dev. 30:118-125. https://doi.org/10.1016/j.braindev.2007.07.003
  30. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. 2002. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 13:4279-4295. https://doi.org/10.1091/mbc.E02-02-0105

Cited by

  1. Hypothermia alleviates hypoxic ischemia-induced dopamine dysfunction and memory impairment in rats vol.15, pp.4, 2010, https://doi.org/10.1080/19768354.2011.607514
  2. Different expression of human GFAP promoter-derived GFP in different subsets of astrocytes in the mouse brain vol.15, pp.4, 2010, https://doi.org/10.1080/19768354.2011.611254
  3. Alcohol exposure induces depression-like behavior by decreasing hippocampal neuronal proliferation through inhibition of the BDNF-ERK pathway in gerbils vol.16, pp.3, 2010, https://doi.org/10.1080/19768354.2011.640352
  4. Treadmill exercise during pregnancy ameliorates post-traumatic stress disorder-induced anxiety-like responses in maternal rats vol.7, pp.2, 2010, https://doi.org/10.3892/mmr.2012.1197