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Bone Marrow Mesenchymal Stem Cell Therapy for Voiding Dysfunction

Regenerative Medicine (A Atala, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Regenerative Medicine

Abstract

Lower urinary tract symptoms can significantly impact quality of life. Current standard treatments are not always effective and are associated with complications and side effects. The discovery of stem cells led to research into cell-based therapies for treatment of disorders of voiding dysfunction. Bone marrow mesenchymal stem cells are particularly promising given their ability to differentiate into a variety of cell types. Recent studies have investigated bone marrow stem cells to treat a number of functional voiding pathologies including bladder outlet obstruction, neurogenic bladder, and stress urinary incontinence. Experiments in tissue regeneration have also attempted to create artificial bladders and urethras. The purpose of this article is to critically review the literature regarding the use of bone marrow mesenchymal stem cells in treatment of voiding dysfunction.

Keywords

Mesenchymal stem cell Bone marrow Voiding dysfunction Lower urinary tract symptoms Incontinence Regenerative medicine 

Abbreviations

BMSC

Bone marrow mesenchymal stem cell

BOO

Bladder outlet obstruction

LPP

Leak point pressure

MSC

Mesenchymal stem cell

SCI

Spinal cord injury

SUI

Stress urinary incontinence

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Alice Yu and Lysanne Campeau each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Hu TW, Wagner TH, Bentkover JD, Leblanc K, Zhou SZ, Hunt T. Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology. 2004;63(3):461–5. doi: 10.1016/j.urology.2003.10.037.PubMedCrossRefGoogle Scholar
  2. 2.
    Weiner LP. Definitions and criteria for stem cells. Methods Mol Biol (Clifton, NJ). 2008;438:3–8. doi: 10.1007/978-1-59745-133-8_1.Google Scholar
  3. 3.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8(4):315–7. doi: 10.1080/14653240600855905.PubMedCrossRefGoogle Scholar
  4. 4.
    Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007;213(2):341–7. doi: 10.1002/jcp.21200.PubMedCrossRefGoogle Scholar
  5. 5.
    Gilbert SM, Lai J, Saigal CS, Gore JL. Downstream complications following urinary diversion. J Urol. 2013;190(3):916–22. doi: 10.1016/j.juro.2013.03.026.PubMedCrossRefGoogle Scholar
  6. 6.
    Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet. 2006;367(9518):1241–6. doi: 10.1016/s0140-6736(06)68438-9.PubMedCrossRefGoogle Scholar
  7. 7.•
    Joseph DB, Borer JG, De Filippo RE, Hodges SJ, McLorie GA. Autologous cell seeded biodegradable scaffold for augmentation cystoplasty: phase II study in children and adolescents with spina bifida. J Urol. 2014;191(5):1389–95. doi: 10.1016/j.juro.2013.10.103. This follow up to the original Atala et al. study demonstrates that there is still much to learn about tissue regeneration. The trial failed to reproduce the results of the original study, and the complication rates of autologous engineered bladders was too high to be considered a safe alternative for now. PubMedCrossRefGoogle Scholar
  8. 8.
    Adamowicz J, Juszczak K, Bajek A, Tworkiewicz J, Nowacki M, Marszalek A, et al. Morphological and urodynamic evaluation of urinary bladder wall regeneration: muscles guarantee contraction but not proper function—a rat model research study. Transplant Proc. 2012;44(5):1429–34. doi: 10.1016/j.transproceed.2012.01.144.PubMedCrossRefGoogle Scholar
  9. 9.
    Sharma AK, Bury MI, Marks AJ, Fuller NJ, Meisner JW, Tapaskar N, et al. A nonhuman primate model for urinary bladder regeneration using autologous sources of bone marrow-derived mesenchymal stem cells. Stem Cells (Dayton, Ohio). 2011;29(2):241–50. doi: 10.1002/stem.568.CrossRefGoogle Scholar
  10. 10.
    Raya-Rivera A, Esquiliano DR, Yoo JJ, Lopez-Bayghen E, Soker S, Atala A. Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet. 2011;377(9772):1175–82. doi: 10.1016/s0140-6736(10)62354-9.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Li CL, Liao WB, Yang SX, Song C, Li YW, Xiong YH, et al. Urethral reconstruction using bone marrow mesenchymal stem cell- and smooth muscle cell-seeded bladder acellular matrix. Transplant Proc. 2013;45(9):3402–7. doi: 10.1016/j.transproceed.2013.07.055.PubMedCrossRefGoogle Scholar
  12. 12.
    Kanno Y, Mitsui T, Sano H, Kitta T, Moriya K, Nonomura K. Contribution of bone marrow-derived mesenchymal stem cells to the morphological changes in the bladder after partial outlet obstruction: a preliminary study. Int J Urol Off J Jpn Urol Assoc. 2014. doi: 10.1111/iju.12406.Google Scholar
  13. 13.
    Tanaka ST, Martinez-Ferrer M, Makari JH, Wills ML, Thomas JC, Adams MC, et al. Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction. J Urol. 2009;182(4 Suppl):1769–74. doi: 10.1016/j.juro.2009.02.081.PubMedCrossRefGoogle Scholar
  14. 14.
    Woo LL, Tanaka ST, Anumanthan G, Pope JC, Thomas JC, Adams MC, et al. Mesenchymal stem cell recruitment and improved bladder function after bladder outlet obstruction: preliminary data. J Urol. 2011;185(3):1132–8. doi: 10.1016/j.juro.2010.10.033.PubMedCrossRefGoogle Scholar
  15. 15.
    Lee HJ, Won JH, Doo SH, Kim JH, Song KY, Lee SJ, et al. Inhibition of collagen deposit in obstructed rat bladder outlet by transplantation of superparamagnetic iron oxide-labeled human mesenchymal stem cells as monitored by molecular magnetic resonance imaging (MRI). Cell Transplant. 2012;21(5):959–70. doi: 10.3727/096368911x627516.PubMedCrossRefGoogle Scholar
  16. 16.
    Song YS, Lee HJ, Doo SH, Lee SJ, Lim I, Chang KT, et al. Mesenchymal stem cells overexpressing hepatocyte growth factor (HGF) inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction. Cell Transplant. 2012;21(8):1641–50. doi: 10.3727/096368912x637488.PubMedCrossRefGoogle Scholar
  17. 17.
    Nishijima S, Sugaya K, Miyazato M, Kadekawa K, Oshiro Y, Uchida A, et al. Restoration of bladder contraction by bone marrow transplantation in rats with underactive bladder. Biomed Res (Tokyo, Jpn). 2007;28(5):275–80.CrossRefGoogle Scholar
  18. 18.
    Dayanc M, Kibar Y, Ural AU, Onguru O, Yildiz O, Irkilata HC, et al. The histopathologic, pharmacologic and urodynamic results of mesenchymal stem cell’s injection into the decompensated rabbit’s bladder. Stem Cell Rev. 2012;8(4):1245–53. doi: 10.1007/s12015-012-9393-4.PubMedCrossRefGoogle Scholar
  19. 19.
    Soler R, Füllhase C, Hanson A, Campeau L, Santos C, Andersson K-E. Stem cell therapy ameliorates bladder dysfunction in an animal model of Parkinson disease. J Urol. 2012;187(4):1491–7. doi: 10.1016/j.juro.2011.11.079.PubMedCrossRefGoogle Scholar
  20. 20.
    Campeau L, Soler R, Sittadjody S, Pareta R, Nomiya M, Zarifpour M, et al. Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on voiding function in a rat model of Parkinson disease. J Urol. 2014;191(3):850–9. doi: 10.1016/j.juro.2013.08.026.PubMedCrossRefGoogle Scholar
  21. 21.
    Park WB, Kim SY, Lee SH, Kim HW, Park JS, Hyun JK. The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats. BMC Neurosci. 2010;11:119. doi: 10.1186/1471-2202-11-119.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res. 2013;1533:73–9. doi: 10.1016/j.brainres.2013.08.016.PubMedCrossRefGoogle Scholar
  23. 23.
    Yazdani SO, Hafizi M, Zali AR, Atashi A, Ashrafi F, Seddighi AS, et al. Safety and possible outcome assessment of autologous Schwann cell and bone marrow mesenchymal stromal cell co-transplantation for treatment of patients with chronic spinal cord injury. Cytotherapy. 2013;15(7):782–91. doi: 10.1016/j.jcyt.2013.03.012.PubMedCrossRefGoogle Scholar
  24. 24.
    Melville JL, Katon W, Delaney K, Newton K. Urinary incontinence in US women: a population-based study. Arch Intern Med. 2005;165(5):537–42. doi: 10.1001/archinte.165.5.537.PubMedCrossRefGoogle Scholar
  25. 25.
    Zou XH, Zhi YL, Chen X, Jin HM, Wang LL, Jiang YZ, et al. Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. Biomaterials. 2010;31(18):4872–9. doi: 10.1016/j.biomaterials.2010.02.056.PubMedCrossRefGoogle Scholar
  26. 26.
    Madjar S, Sharma AK, Waltzer WC, Frischer Z, Secrest CL. Periurethral mass formations following bulking agent injection for the treatment of urinary incontinence. J Urol. 2006;175(4):1408–10. doi: 10.1016/s0022-5347(05)00679-8.PubMedCrossRefGoogle Scholar
  27. 27.•
    Gunetti M, Tomasi S, Giammò A, Boido M, Rustichelli D, Mareschi K, et al. Myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo or usage in urinary incontinence. PLoS ONE. 2012;7(9):e45538. doi: 10.1371/journal.pone.0045538. This unique study characterises the interaction between BMSC and muscle cells. It appears that BMSC serves as a promoter cell rather than differentiate into muscle cells after injection into perineal tissue. This is particularly significant as better understanding of basic cell biology and behaviour is key to utilising stem cells in tissue regeneration. PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    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. doi: 10.1002/nau.20998.PubMedCrossRefGoogle Scholar
  29. 29.
    Du X-W, Wu H-L, Zhu Y-F, Hu J-B, Jin F, Lv R-P, et al. Experimental study of therapy of bone marrow mesenchymal stem cells or muscle-like cells/calcium alginate composite gel for the treatment of stress urinary incontinence. Neurourol Urodyn. 2013;32(3):281–6. doi: 10.1002/nau.22291.PubMedCrossRefGoogle Scholar
  30. 30.••
    Peters KM, Dmochowski RR, Carr LK, Robert M, Kaufman MR, Sirls LT, et al. Autologous muscle derived cells for treatment of stress urinary incontinence in women. J Urol. 2014;192(2):469–76. doi: 10.1016/j.juro.2014.02.047. Although this study does not describe using BMSC per se, it is the largest clinical trial to date utilizing stem cell therapy in voiding dysfunction. Not only are the results promising, the study also demonstrate relative long-term safety (12 months). PubMedCrossRefGoogle Scholar
  31. 31.
    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. doi: 10.1155/2012/612946.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Trainor N, Pietak A, Smith T. Rethinking clinical delivery of adult stem cell therapies. Nat Biotechnol. 2014;32(8):729–35. doi: 10.1038/nbt.2970.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Division of Urology, Department of Surgery, Jewish General HospitalMcGill UniversityMontrealCanada

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