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Stem Cell Therapy in Spinal Cord Injury-Induced Neurogenic Lower Urinary Tract Dysfunction

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Abstract

Spinal cord injury (SCI) is a devastating condition that enormously affects an individual’s health and quality of life. Neurogenic lower urinary tract dysfunction (NLUTD) is one of the most important sequelae induced by SCI, causing complications including urinary tract infection, renal function deterioration, urinary incontinence, and voiding dysfunction. Current therapeutic methods for SCI-induced NLUTD mainly target on the urinary bladder, but the outcomes are still far from satisfactory. Stem cell therapy has gained increasing attention for years for its ability to rescue the injured spinal cord directly. Stem cell differentiation and their paracrine effects, including exosomes, are the proposed mechanisms to enhance the recovery from SCI. Several animal studies have demonstrated improvement in bladder function using mesenchymal stem cells (MSCs) and neural stem cells (NSCs). Human clinical trials also provide promising results in urodynamic parameters after MSC therapy. However, there is still uncertainty about the ideal treatment window and application protocol for stem cell therapy. Besides, data on the therapeutic effects regarding NSCs and stem cell-derived exosomes in SCI-related NLUTD are scarce. Therefore, there is a pressing need for further well-designed human clinical trials to translate the stem cell therapy into a formal therapeutic option for SCI-induced NLUTD.

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Abbreviations

SCI:

Spinal cord injury

NLUTD:

Neurogenic lower urinary tract dysfunction

MSCs:

Mesenchymal stem cells

NSCs:

Neural stem cells

ESCs:

Embryonic stem cells

iPSCs:

Induced pluripotent stem cells

OECs:

Olfactory ensheathing cells

BM-MSCs:

Mesenchymal stem cells from bone marrow

UC-MSCs:

Mesenchymal stem cells from umbilical cord

BMSCs:

Bone marrow stromal cells

NVC:

Non-voiding contraction

PVR:

Post-void residual volume

EMG:

Electromyography

hMSC:

Human mesenchymal stem cells

hADSCs:

Human adipose-derived stem cells

hAFSCs:

Human amniotic fluid-derived stem cells

OMSCs:

Oral mucosa stem cells

hpMSC:

Human placental mesenchymal stem cell

CNS:

Central nervous system

NRPs:

Neuronal-restricted pro-genitors

GRPs:

Glia-restricted progenitors

iNSCs:

Induced neural stem cells

NBQX:

2,3-dioxo-6-nitro-7-sulfamoyl-benzo[f]quinoxaline

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

hGRP:

Human glia-restricted progenitor

hGDA:

Astrocytes from human glia-restricted progenitor

Pdet:

Detrusor contraction pressure

WJ-MSCs:

Wharton’s jelly mesenchymal stromal cells

ADSCs:

Adipose-derived stem cells

References

  1. Sekhon, L. H., & Fehlings, M. G. (2001). Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976), 26, S2–12.

    CAS  PubMed  Google Scholar 

  2. Ahuja, C. S., Wilson, J. R., Nori, S., et al. (2017). Traumatic spinal cord injury. Nat Rev Dis Primers, 3, 17018.

    PubMed  Google Scholar 

  3. Kumar, R., Lim, J., Mekary, R. A., et al. (2018). Traumatic spinal Injury: Global Epidemiology and Worldwide volume. World Neurosurg, 113, e345–e363.

    PubMed  Google Scholar 

  4. Krassioukov, A., Warburton, D. E., Teasell, R., & Eng, J. J. (2009). A systematic review of the management of autonomic dysreflexia after spinal cord injury. Archives Of Physical Medicine And Rehabilitation, 90, 682–695.

    PubMed  PubMed Central  Google Scholar 

  5. McDonald, J. W., & Sadowsky, C. (2002). Spinal-cord injury. Lancet, 359, 417–425.

    PubMed  Google Scholar 

  6. Assinck, P., Duncan, G. J., Hilton, B. J., Plemel, J. R., & Tetzlaff, W. (2017). Cell transplantation therapy for spinal cord injury. Nature Neuroscience, 20, 637–647.

    CAS  PubMed  Google Scholar 

  7. Cofano, F., Boido, M., Monticelli, M. (2019). Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy.Int J Mol Sci,20.

  8. Wilson, J. R., Tetreault, L. A., Kwon, B. K., et al. (2017). Timing of decompression in patients with Acute spinal cord Injury: A systematic review. Global Spine J, 7, 95s–115s.

    PubMed  PubMed Central  Google Scholar 

  9. Yılmaz, T., & Kaptanoğlu, E. (2015). Current and future medical therapeutic strategies for the functional repair of spinal cord injury. World J Orthop, 6, 42–55.

    PubMed  PubMed Central  Google Scholar 

  10. Benevento, B. T., & Sipski, M. L. (2002). Neurogenic bladder, neurogenic bowel, and sexual dysfunction in people with spinal cord injury. Physical Therapy, 82, 601–612.

    PubMed  Google Scholar 

  11. Taweel, W. A., & Seyam, R. (2015). Neurogenic bladder in spinal cord injury patients. Res Rep Urol, 7, 85–99.

    PubMed  PubMed Central  Google Scholar 

  12. Groen, J., Pannek, J., Castro Diaz, D., et al. (2016). Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology. European Urology, 69, 324–333.

    PubMed  Google Scholar 

  13. Kriz, J., Sediva, K., & Maly, M. (2021). Causes of death after spinal cord injury in the Czech Republic. Spinal Cord, 59, 814–820.

    PubMed  Google Scholar 

  14. Savic, G., DeVivo, M. J., Frankel, H. L., et al. (2017). Causes of death after traumatic spinal cord injury-a 70-year british study. Spinal Cord, 55, 891–897.

    CAS  PubMed  Google Scholar 

  15. Chamberlain, J. D., Meier, S., Mader, L., von Groote, P. M., & Brinkhof, M. W. (2015). Mortality and longevity after a spinal cord injury: Systematic review and meta-analysis. Neuroepidemiology, 44, 182–198.

    PubMed  Google Scholar 

  16. Gamé, X., Castel-Lacanal, E., Bentaleb, Y., et al. (2008). Botulinum toxin a detrusor injections in patients with neurogenic detrusor overactivity significantly decrease the incidence of symptomatic urinary tract infections. European Urology, 53, 613–618.

    PubMed  Google Scholar 

  17. Frankel, H. L., Coll, J. R., Charlifue, S. W., et al. (1998). Long-term survival in spinal cord injury: A fifty year investigation. Spinal Cord, 36, 266–274.

    CAS  PubMed  Google Scholar 

  18. Jamil, F. (2001). Towards a catheter free status in neurogenic bladder dysfunction: A review of bladder management options in spinal cord injury (SCI). Spinal Cord, 39, 355–361.

    CAS  PubMed  Google Scholar 

  19. Madersbacher, H., Mürtz, G., & Stöhrer, M. (2013). Neurogenic detrusor overactivity in adults: A review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord, 51, 432–441.

    CAS  PubMed  Google Scholar 

  20. Madhuvrata, P., Singh, M., Hasafa, Z., & Abdel-Fattah, M. (2012). Anticholinergic drugs for adult neurogenic detrusor overactivity: A systematic review and meta-analysis. European Urology, 62, 816–830.

    CAS  PubMed  Google Scholar 

  21. Krhut, J., Borovička, V., Bílková, K., et al. (2018). Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-Prospective, randomized, double-blind, placebo-controlled study. Neurourology And Urodynamics, 37, 2226–2233.

    CAS  PubMed  Google Scholar 

  22. Yuan, H., Cui, Y., Wu, J., et al. (2017). Efficacy and adverse events Associated with Use of OnabotulinumtoxinA for treatment of neurogenic detrusor overactivity: A Meta-analysis. Int Neurourol J, 21, 53–61.

    PubMed  PubMed Central  Google Scholar 

  23. Cheng, T., Shuang, W. B., Jia, D. D., et al. (2016). Efficacy and safety of OnabotulinumtoxinA in patients with neurogenic detrusor overactivity: A systematic review and Meta-analysis of Randomized controlled trials. PLoS One, 11, e0159307.

    PubMed  PubMed Central  Google Scholar 

  24. Chen, S. F., & Kuo, H. C. (2021). Will repeated botulinum toxin a improve detrusor overactivity and bladder compliance in patients with chronic spinal cord injury? Tzu Chi Med J, 33, 101–107.

    PubMed  Google Scholar 

  25. Stöhrer, M., Kramer, G., Goepel, M., et al. (1997). Bladder autoaugmentation in adult patients with neurogenic voiding dysfunction. Spinal Cord, 35, 456–462.

    PubMed  Google Scholar 

  26. Krebs, J., Bartel, P., & Pannek, J. (2016). Functional outcome of supratrigonal cystectomy and augmentation ileocystoplasty in adult patients with refractory neurogenic lower urinary tract dysfunction. Neurourology And Urodynamics, 35, 260–266.

    PubMed  Google Scholar 

  27. Wyndaele, J. J., Birch, B., Borau, A., et al. (2018). Surgical management of the neurogenic bladder after spinal cord injury. World Journal Of Urology, 36, 1569–1576.

    PubMed  Google Scholar 

  28. Moro, C., Phelps, C., Veer, V., et al. (2022). The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis. Neurourology And Urodynamics, 41, 127–139.

    CAS  PubMed  Google Scholar 

  29. Abrams, P., Amarenco, G., Bakke, A., et al. (2003). Tamsulosin: Efficacy and safety in patients with neurogenic lower urinary tract dysfunction due to suprasacral spinal cord injury. Journal Of Urology, 170, 1242–1251.

    PubMed  Google Scholar 

  30. Stoffel, J. T. (2016). Detrusor sphincter dyssynergia: A review of physiology, diagnosis, and treatment strategies. Transl Androl Urol, 5, 127–135.

    PubMed  PubMed Central  Google Scholar 

  31. Kao, Y. L., Huang, K. H., Kuo, H. C., & Ou, Y. C. (2019). The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction. Toxins (Basel), 11.

  32. Ou, Y. C., Huang, K. H., Jan, H. C. (2021). Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.Toxins (Basel),13.

  33. Prieto, J., Murphy, C. L., Moore, K. N., & Fader, M. (2014). Intermittent catheterisation for long-term bladder management.Cochrane Database Syst Rev:Cd006008.

  34. Sharif-Alhoseini, M., Khormali, M., Rezaei, M., et al. (2017). Animal models of spinal cord injury: A systematic review. Spinal Cord, 55, 714–721.

    CAS  PubMed  Google Scholar 

  35. Lilley, E., Andrews, M. R., Bradbury, E. J., et al. (2020). Refining rodent models of spinal cord injury. Experimental Neurology, 328, 113273.

    PubMed  Google Scholar 

  36. Andersson, K. E., Soler, R., & Füllhase, C. (2011). Rodent models for urodynamic investigation. Neurourology And Urodynamics, 30, 636–646.

    PubMed  Google Scholar 

  37. Park, W. B., Kim, S. Y., Lee, S. H., et al. (2010). The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats. Bmc Neuroscience, 11, 119.

    PubMed  PubMed Central  Google Scholar 

  38. Fandel, T. M., Trivedi, A., Nicholas, C. R., et al. (2016). Transplanted human stem cell-derived Interneuron Precursors Mitigate mouse bladder dysfunction and Central Neuropathic Pain after spinal cord Injury. Cell Stem Cell, 19, 544–557.

    CAS  PubMed  Google Scholar 

  39. Yousefifard, M., Rahimi-Movaghar, V., Nasirinezhad, F., et al. (2016). Neural stem/progenitor cell transplantation for spinal cord injury treatment; a systematic review and meta-analysis. Neuroscience, 322, 377–397.

    CAS  PubMed  Google Scholar 

  40. Mothe, A. J., & Tator, C. H. (2013). Review of transplantation of neural stem/progenitor cells for spinal cord injury. International Journal Of Developmental Neuroscience, 31, 701–713.

    CAS  PubMed  Google Scholar 

  41. Geffner, L. F., Santacruz, P., Izurieta, M., et al. (2008). Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: Comprehensive case studies. Cell Transplantation, 17, 1277–1293.

    CAS  PubMed  Google Scholar 

  42. Fan, X., Wang, J. Z., Lin, X. M., & Zhang, L. (2017). Stem cell transplantation for spinal cord injury: A meta-analysis of treatment effectiveness and safety. Neural Regen Res, 12, 815–825.

    PubMed  PubMed Central  Google Scholar 

  43. Weissman, I. L., Anderson, D. J., & Gage, F. (2001). Stem and progenitor cells: Origins, phenotypes, lineage commitments, and transdifferentiations. Annual Review Of Cell And Developmental Biology, 17, 387–403.

    CAS  PubMed  Google Scholar 

  44. Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: Past, present, and future. Stem Cell Research & Therapy, 10, 68.

    CAS  Google Scholar 

  45. Ullah, I., Subbarao, R. B., & Rho, G. J. (2015). Human mesenchymal stem cells - current trends and future prospective.Biosci Rep,35.

  46. Tang, Y., Yu, P., & Cheng, L. (2017). Current progress in the derivation and therapeutic application of neural stem cells. Cell Death And Disease, 8, e3108.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Tator, C. H., & Fehlings, M. G. (1991). Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. Case Report Journal Of Neurosurgery, 75, 15–26.

    CAS  Google Scholar 

  48. Oyinbo, C. A. (2011). Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade. Acta Neurobiol Exp (Wars), 71, 281–299.

    PubMed  Google Scholar 

  49. Hawryluk, G. W., Mothe, A., Wang, J., et al. (2012). An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells And Development, 21, 2222–2238.

    CAS  PubMed  Google Scholar 

  50. Gu, W., Zhang, F., Xue, Q., et al. (2010). Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord. Neuropathology, 30, 205–217.

    PubMed  Google Scholar 

  51. Zhang, S. X., Huang, F., Gates, M., & Holmberg, E. G. (2013). Role of endogenous Schwann cells in tissue repair after spinal cord injury. Neural Regen Res, 8, 177–185.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Seo, J. H., & Cho, S. R. (2012). Neurorestoration induced by mesenchymal stem cells: Potential therapeutic mechanisms for clinical trials. Yonsei Medical Journal, 53, 1059–1067.

    PubMed  PubMed Central  Google Scholar 

  53. Li, Z., Guo, G. H., Wang, G. S., Guan, C. X., & Yue, L. (2014). Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Genetics And Molecular Research, 13, 6083–6092.

    CAS  PubMed  Google Scholar 

  54. Yu, S., Yao, S., Wen, Y., et al. (2016). Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats. Scientific Reports, 6, 33428.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Stokes, B. T., & Reier, P. J. (1991). Oxygen transport in intraspinal fetal grafts: Graft-host relations. Experimental Neurology, 111, 312–323.

    CAS  PubMed  Google Scholar 

  56. Han, D., Chen, S., Fang, S., et al. (2017). The neuroprotective Effects of muscle-derived stem cells via brain-derived neurotrophic factor in spinal cord Injury Model. Biomed Research International, 2017, 1972608.

    PubMed  PubMed Central  Google Scholar 

  57. Wang, C., Shi, D., Song, X., et al. (2016). Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation. Neurochemistry International, 97, 15–25.

    CAS  PubMed  Google Scholar 

  58. Sabelström, H., Stenudd, M., Réu, P., et al. (2013). Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice. Science, 342, 637–640.

    PubMed  Google Scholar 

  59. Cheng, Z., Zhu, W., Cao, K. (2016). Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.Int J Mol Sci, 17.

  60. Nakajima, H., Uchida, K., Guerrero, A. R., et al. (2012). Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. Journal Of Neurotrauma, 29, 1614–1625.

    PubMed  PubMed Central  Google Scholar 

  61. Abrams, M. B., Dominguez, C., Pernold, K., et al. (2009). Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury. Restorative Neurology And Neuroscience, 27, 307–321.

    PubMed  Google Scholar 

  62. Barnabé-Heider, F., & Frisén, J. (2008). Stem cells for spinal cord repair. Cell Stem Cell, 3, 16–24.

    PubMed  Google Scholar 

  63. Xu, X. M., Guénard, V., Kleitman, N., & Bunge, M. B. (1995). Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. The Journal Of Comparative Neurology, 351, 145–160.

    CAS  PubMed  Google Scholar 

  64. Takeoka, A., **drich, D. L., Muñoz-Quiles, C., et al. (2011). Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation. Journal Of Neuroscience, 31, 4298–4310.

    CAS  PubMed  Google Scholar 

  65. Lu, P., Wang, Y., Graham, L., et al. (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150, 1264–1273.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Lu, P., Yang, H., Jones, L. L., Filbin, M. T., & Tuszynski, M. H. (2004). Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. Journal Of Neuroscience, 24, 6402–6409.

    CAS  PubMed  Google Scholar 

  67. Xu, X. M., Chen, A., Guénard, V., Kleitman, N., & Bunge, M. B. (1997). Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. Journal Of Neurocytology, 26, 1–16.

    CAS  PubMed  Google Scholar 

  68. Bradbury, E. J., & Burnside, E. R. (2019). Moving beyond the glial scar for spinal cord repair. Nature Communications, 10, 3879.

    PubMed  PubMed Central  Google Scholar 

  69. Filous, A. R., & Silver, J. (2016). Targeting astrocytes in CNS injury and disease: A translational research approach. Progress In Neurobiology, 144, 173–187.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Burda, J. E., & Sofroniew, M. V. (2014). Reactive gliosis and the multicellular response to CNS damage and disease. Neuron, 81, 229–248.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Stenudd, M., Sabelström, H., & Frisén, J. (2015). Role of endogenous neural stem cells in spinal cord injury and repair. JAMA Neurol, 72, 235–237.

    PubMed  Google Scholar 

  72. **ao, L., Saiki, C., & Ide, R. (2014). Stem cell therapy for central nerve system injuries: Glial cells hold the key. Neural Regen Res, 9, 1253–1260.

    PubMed  PubMed Central  Google Scholar 

  73. Emery, E., Aldana, P., Bunge, M. B., et al. (1998). Apoptosis after traumatic human spinal cord injury. Case Report Journal Of Neurosurgery, 89, 911–920.

    CAS  Google Scholar 

  74. Waxman, S. G. (1989). Demyelination in spinal cord injury. Journal Of The Neurological Sciences, 91, 1–14.

    CAS  PubMed  Google Scholar 

  75. Tetzlaff, W., Okon, E. B., Karimi-Abdolrezaee, S., et al. (2011). A systematic review of cellular transplantation therapies for spinal cord injury. Journal Of Neurotrauma, 28, 1611–1682.

    PubMed  PubMed Central  Google Scholar 

  76. Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.

    CAS  PubMed  Google Scholar 

  77. Wagner, W., Wein, F., Seckinger, A., et al. (2005). Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Experimental Hematology, 33, 1402–1416.

    CAS  PubMed  Google Scholar 

  78. Charbord, P. (2010). Bone marrow mesenchymal stem cells: Historical overview and concepts. Human Gene Therapy, 21, 1045–1056.

    CAS  PubMed  Google Scholar 

  79. Minteer, D., Marra, K. G., & Rubin, J. P. (2013). Adipose-derived mesenchymal stem cells: Biology and potential applications. Advances In Biochemical Engineering/Biotechnology, 129, 59–71.

    CAS  PubMed  Google Scholar 

  80. Nagamura-Inoue, T., & He, H. (2014). Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility. World J Stem Cells, 6, 195–202.

    PubMed  PubMed Central  Google Scholar 

  81. Loukogeorgakis, S. P., & De Coppi, P. (2017). Concise Review: Amniotic fluid stem cells: The known, the unknown, and potential regenerative medicine applications. Stem Cells, 35, 1663–1673.

    PubMed  Google Scholar 

  82. Savickiene, J., Treigyte, G., Baronaite, S., et al. (2015). Human amniotic fluid mesenchymal stem cells from second- and third-trimester amniocentesis: Differentiation potential, molecular signature, and Proteome Analysis. Stem Cells Int, 2015, 319238.

    PubMed  PubMed Central  Google Scholar 

  83. Moraghebi, R., Kirkeby, A., Chaves, P., et al. (2017). Term amniotic fluid: An unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications. Stem Cell Research & Therapy, 8, 190.

    Google Scholar 

  84. Sessarego, N., Parodi, A., Podestà, M., et al. (2008). Multipotent mesenchymal stromal cells from amniotic fluid: Solid perspectives for clinical application. Haematologica, 93, 339–346.

    PubMed  Google Scholar 

  85. Hou, T., Xu, J., Wu, X., et al. (2009). Umbilical cord Wharton’s Jelly: A new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Engineering Part A, 15, 2325–2334.

    CAS  PubMed  Google Scholar 

  86. Marino, L., Castaldi, M. A., Rosamilio, R., et al. (2019). Mesenchymal stem cells from the Wharton’s Jelly of the human umbilical cord: Biological Properties and therapeutic potential. Int J Stem Cells, 12, 218–226.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Wang, H. S., Hung, S. C., Peng, S. T., et al. (2004). Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells, 22, 1330–1337.

    PubMed  Google Scholar 

  88. Bartsch, G., Yoo, J. J., De Coppi, P., et al. (2005). Propagation, expansion, and multilineage differentiation of human somatic stem cells from dermal progenitors. Stem Cells And Development, 14, 337–348.

    CAS  PubMed  Google Scholar 

  89. Riekstina, U., Muceniece, R., Cakstina, I., Muiznieks, I., & Ancans, J. (2008). Characterization of human skin-derived mesenchymal stem cell proliferation rate in different growth conditions. Cytotechnology, 58, 153–162.

    CAS  PubMed  Google Scholar 

  90. Sharpe, P. T. (2016). Dental mesenchymal stem cells. Development, 143, 2273–2280.

    CAS  PubMed  Google Scholar 

  91. Huang, G. T., Gronthos, S., & Shi, S. (2009). Mesenchymal stem cells derived from dental tissues vs. those from other sources: Their biology and role in regenerative medicine. Journal Of Dental Research, 88, 792–806.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Ledesma-Martínez, E., Mendoza-Núñez, V. M., & Santiago-Osorio, E. (2016). Mesenchymal Stem Cells Derived from Dental Pulp: A Review. Stem Cells Int, 2016:4709572.

  93. Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., et al. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Experimental Neurology, 164, 247–256.

    CAS  PubMed  Google Scholar 

  94. Qi, X., Shao, M., Peng, H., et al. (2010). In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system. Journal Of Clinical Neuroscience : Official Journal Of The Neurosurgical Society Of Australasia, 17, 908–913.

    CAS  PubMed  Google Scholar 

  95. Sorrell, J. M., Baber, M. A., & Caplan, A. I. (2009). Influence of adult mesenchymal stem cells on in vitro vascular formation. Tissue Engineering Part A, 15, 1751–1761.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Rehman, J., Traktuev, D., Li, J., et al. (2004). Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation, 109, 1292–1298.

    PubMed  Google Scholar 

  97. Hofer, H. R., & Tuan, R. S. (2016). Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Research & Therapy, 7, 131.

    Google Scholar 

  98. Temeltas, G., Dagci, T., Kurt, F., Evren, V., & Tuglu, I. (2009). Bladder function recovery in rats with traumatic spinal cord injury after transplantation of neuronal-glial restricted precursors or bone marrow stromal cells. Journal Of Urology, 181, 2774–2779.

    PubMed  Google Scholar 

  99. Hu, Y., Liao, L. M., Ju, Y. H., et al. (2012). Intravenously transplanted bone marrow stromal cells promote recovery of lower urinary tract function in rats with complete spinal cord injury. Spinal Cord, 50, 202–207.

    CAS  PubMed  Google Scholar 

  100. Lee, H. J., An, J., Doo, S. W., et al. (2015). Improvement in spinal cord Injury-Induced bladder fibrosis using mesenchymal stem cell transplantation into the bladder wall. Cell Transplantation, 24, 1253–1263.

    CAS  PubMed  Google Scholar 

  101. Salehi-Pourmehr, H., Rahbarghazi, R., Mahmoudi, J., et al. (2019). Intra-bladder wall transplantation of bone marrow mesenchymal stem cells improved urinary bladder dysfunction following spinal cord injury. Life Sciences, 221, 20–28.

    CAS  PubMed  Google Scholar 

  102. Romero-Ramírez, L., Wu, S., de Munter, J., et al. (2020). Treatment of rats with spinal cord injury using human bone marrow-derived stromal cells prepared by negative selection. Journal Of Biomedical Science, 27, 35.

    PubMed  PubMed Central  Google Scholar 

  103. Sandner, B., Ciatipis, M., Motsch, M., et al. (2016). Limited Functional Effects of Subacute Syngeneic Bone Marrow Stromal Cell Transplantation after Rat spinal cord Contusion Injury. Cell Transplantation, 25, 125–139.

    PubMed  Google Scholar 

  104. Erdogan, B., Yaycioglu, O., Feride Sahin, I., et al. (2013). The effects of fetal allogeneic umbilical cord tissue transplant following experimental spinal cord injury on urinary bladder morphology. Case Report Neurologia I Neurochirurgia Polska, 47, 138–144.

    Google Scholar 

  105. Villanova Junior, J. A., Fracaro, L., Rebelatto, C. L. K., et al. (2020). Recovery of motricity and micturition after transplantation of mesenchymal stem cells in rats subjected to spinal cord injury. Neuroscience Letters, 734, 135134.

    CAS  PubMed  Google Scholar 

  106. Liang, C. C., Shaw, S. S., Ko, Y. S., Huang, Y. H., & Lee, T. H. (2020). Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats. Scientific Reports, 10, 10030.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Szpaderska, A. M., Zuckerman, J. D., & DiPietro, L. A. (2003). Differential injury responses in oral mucosal and cutaneous wounds. Journal Of Dental Research, 82, 621–626.

    CAS  PubMed  Google Scholar 

  108. López, S., Hoz, L., Tenorio, E. P. (2021). Can Human Oral Mucosa Stem Cells Differentiate to Corneal Epithelia?Int J Mol Sci, 22.

  109. Marynka-Kalmani, K., Treves, S., Yafee, M., et al. (2010). The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells, 28, 984–995.

    CAS  PubMed  Google Scholar 

  110. Cho, Y. S., Ko, I. G., Kim, S. E., et al. (2014). Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats. Journal Of Biomedical Science, 21, 43.

    PubMed  PubMed Central  Google Scholar 

  111. McKay, R. (1997). Stem cells in the central nervous system. Science, 276, 66–71.

    CAS  PubMed  Google Scholar 

  112. Reynolds, B. A., & Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 255, 1707–1710.

    CAS  PubMed  Google Scholar 

  113. Temple, S. (2001). The development of neural stem cells. Nature, 414, 112–117.

    CAS  PubMed  Google Scholar 

  114. Rao, M. S. (1999). Multipotent and restricted precursors in the central nervous system. Anatomical Record, 257, 137–148.

    CAS  PubMed  Google Scholar 

  115. Wen, S., Li, H., & Liu, J. (2009). Dynamic signaling for neural stem cell fate determination. Cell Adh Migr, 3, 107–117.

    PubMed  PubMed Central  Google Scholar 

  116. Conti, L., & Cattaneo, E. (2010). Neural stem cell systems: Physiological players or in vitro entities? Nature Reviews Neuroscience, 11, 176–187.

    CAS  PubMed  Google Scholar 

  117. Kim, S. M., Flaßkamp, H., Hermann, A., et al. (2014). Direct conversion of mouse fibroblasts into induced neural stem cells. Nature Protocols, 9, 871–881.

    CAS  PubMed  Google Scholar 

  118. Han, D. W., Tapia, N., Hermann, A., et al. (2012). Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell, 10, 465–472.

    CAS  PubMed  Google Scholar 

  119. Thier, M., Wörsdörfer, P., Lakes, Y. B., et al. (2012). Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell, 10, 473–479.

    CAS  PubMed  Google Scholar 

  120. Fu, L., Zhu, L., Huang, Y., et al. (2008). Derivation of neural stem cells from mesenchymal stemcells: Evidence for a bipotential stem cell population. Stem Cells And Development, 17, 1109–1121.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Woodbury, D., Schwarz, E. J., Prockop, D. J., & Black, I. B. (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. Journal Of Neuroscience Research, 61, 364–370.

    CAS  PubMed  Google Scholar 

  122. Zhao, L. R., Duan, W. M., Reyes, M., et al. (2002). Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Experimental Neurology, 174, 11–20.

    PubMed  Google Scholar 

  123. Buzańska, L., Machaj, E. K., Zabłocka, B., Pojda, Z., & Domańska-Janik, K. (2002). Human cord blood-derived cells attain neuronal and glial features in vitro. Journal Of Cell Science, 115, 2131–2138.

    PubMed  Google Scholar 

  124. Nemati, S. N., Jabbari, R., Ha**asrollah, M., et al. (2014). Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys. Cell J, 16, 117–130.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Einstein, O., & Ben-Hur, T. (2008). The changing face of neural stem cell therapy in neurologic diseases. Archives Of Neurology, 65, 452–456.

    PubMed  Google Scholar 

  126. Mitsui, T., Kakizaki, H., Tanaka, H., et al. (2003). Immortalized neural stem cells transplanted into the injured spinal cord promote recovery of voiding function in the rat. Journal Of Urology, 170, 1421–1425.

    PubMed  Google Scholar 

  127. Neuhuber, B., Barshinger, A. L., Paul, C., et al. (2008). Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord. Journal Of Neurosurgery. Spine, 9, 390–399.

    PubMed  Google Scholar 

  128. Hong, J. Y., Lee, S. H., Lee, S. C., et al. (2014). Therapeutic potential of induced neural stem cells for spinal cord injury. Journal Of Biological Chemistry, 289, 32512–32525.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Mitsui, T., Neuhuber, B., & Fischer, I. (2011). Acute administration of AMPA/Kainate blocker combined with delayed transplantation of neural precursors improves lower urinary tract function in spinal injured rats. Brain Research, 1418, 23–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. **, Y., Neuhuber, B., Singh, A., et al. (2011). Transplantation of human glial restricted progenitors and derived astrocytes into a contusion model of spinal cord injury. Journal Of Neurotrauma, 28, 579–594.

    PubMed  PubMed Central  Google Scholar 

  131. Barakat, D. J., Gaglani, S. M., Neravetla, S. R., et al. (2005). Survival, integration, and axon growth support of glia transplanted into the chronically contused spinal cord. Cell Transplantation, 14, 225–240.

    CAS  PubMed  Google Scholar 

  132. Lu, P., Jones, L. L., & Tuszynski, M. H. (2007). Axon regeneration through scars and into sites of chronic spinal cord injury. Experimental Neurology, 203, 8–21.

    CAS  PubMed  Google Scholar 

  133. Tom, V. J., Sandrow-Feinberg, H. R., Miller, K., et al. (2009). Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord. Journal Of Neuroscience, 29, 14881–14890.

    CAS  PubMed  Google Scholar 

  134. **, Y., Bouyer, J., Shumsky, J. S., Haas, C., & Fischer, I. (2016). Transplantation of neural progenitor cells in chronic spinal cord injury. Neuroscience, 320, 69–82.

    CAS  PubMed  Google Scholar 

  135. de Groat, W. C., Griffiths, D., & Yoshimura, N. (2015). Neural control of the lower urinary tract. Compr Physiol, 5, 327–396.

    PubMed  PubMed Central  Google Scholar 

  136. Kuner, R. (2010). Central mechanisms of pathological pain. Nature Medicine, 16, 1258–1266.

    CAS  PubMed  Google Scholar 

  137. Liu, W. Z., Ma, Z. J., Li, J. R., & Kang, X. W. (2021). Mesenchymal stem cell-derived exosomes: Therapeutic opportunities and challenges for spinal cord injury. Stem Cell Research & Therapy, 12, 102.

    CAS  Google Scholar 

  138. Yang, Z. L., Rao, J., Lin, F. B., et al. (2022). The role of Exosomes and Exosomal noncoding RNAs from different cell sources in spinal cord Injury. Frontiers In Cellular Neuroscience, 16, 882306.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Lai, R. C., Yeo, R. W., & Lim, S. K. (2015). Mesenchymal stem cell exosomes. Seminars In Cell & Developmental Biology, 40, 82–88.

    CAS  Google Scholar 

  140. Février, B., & Raposo, G. (2004). Exosomes: Endosomal-derived vesicles ship** extracellular messages. Current Opinion In Cell Biology, 16, 415–421.

    PubMed  Google Scholar 

  141. Théry, C., Amigorena, S., Raposo, G., & Clayton, A. (2006). Isolation and characterization of exosomes from cell culture supernatants and biological fluids.Curr Protoc Cell Biol, Chap. 3:Unit 3.22.

  142. Kalluri, R., & LeBleu, V. S. (2016). Discovery of double-stranded genomic DNA in circulating exosomes. Cold Spring Harbor Symposia On Quantitative Biology, 81, 275–280.

    PubMed  Google Scholar 

  143. Gimona, M., Pachler, K., Laner-Plamberger, S., Schallmoser, K., & Rohde, E. (2017). Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.Int J Mol Sci, 18.

  144. Liu, W., Wang, Y., Gong, F., et al. (2019). Exosomes Derived from Bone mesenchymal stem cells repair traumatic spinal cord Injury by suppressing the activation of A1 neurotoxic reactive astrocytes. Journal Of Neurotrauma, 36, 469–484.

    PubMed  Google Scholar 

  145. Zhou, Y., Wen, L. L., Li, Y. F., et al. (2022). Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis. Neural Regen Res, 17, 194–202.

    CAS  PubMed  Google Scholar 

  146. Gu, J., **, Z. S., Wang, C. M., et al. (2020). Bone marrow mesenchymal stem cell-derived Exosomes improves spinal cord function after Injury in rats by activating Autophagy. Drug Design, Development And Therapy, 14, 1621–1631.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Zhou, W., Silva, M., Feng, C., et al. (2021). Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis. Stem Cell Research & Therapy, 12, 174.

    Google Scholar 

  148. Zhang, C., Zhang, C., Xu, Y., et al. (2020). Exosomes derived from human placenta-derived mesenchymal stem cells improve neurologic function by promoting angiogenesis after spinal cord injury. Neuroscience Letters, 739, 135399.

    CAS  PubMed  Google Scholar 

  149. Nikfarjam, S., Rezaie, J., Zolbanin, N. M., & Jafari, R. (2020). Mesenchymal stem cell derived-exosomes: A modern approach in translational medicine. Journal of Translational Medicine, 18, 449.

    PubMed  PubMed Central  Google Scholar 

  150. Ren, Z., Qi, Y., Sun, S., Tao, Y., & Shi, R. (2020). Mesenchymal stem cell-derived Exosomes: Hope for spinal cord Injury Repair. Stem Cells And Development, 29, 1467–1478.

    CAS  PubMed  Google Scholar 

  151. Colombo, M., Raposo, G., & Théry, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review Of Cell And Developmental Biology, 30, 255–289.

    CAS  PubMed  Google Scholar 

  152. Rong, Y., Liu, W., Wang, J., et al. (2019). Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell Death And Disease, 10, 340.

    PubMed  PubMed Central  Google Scholar 

  153. Zhou, W., Silva, M., Feng, C., et al. (2021). Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis. Stem Cell Research & Therapy, 12, 174.

    Google Scholar 

  154. Chen, Y., He, Y., & DeVivo, M. J. (2016). Changing demographics and Injury Profile of New Traumatic spinal cord injuries in the United States, 1972–2014. Archives Of Physical Medicine And Rehabilitation, 97, 1610–1619.

    PubMed  Google Scholar 

  155. Streng, T., Talo, A., & Andersson, K. E. (2004). Transmitters contributing to the voiding contraction in female rats. Bju International, 94, 910–914.

    PubMed  Google Scholar 

  156. Andersson, K. E., & Arner, A. (2004). Urinary bladder contraction and relaxation: Physiology and pathophysiology. Physiological Reviews, 84, 935–986.

    CAS  PubMed  Google Scholar 

  157. Blaivas, J. G. (1996). The bladder is an unreliable witness. Neurourology And Urodynamics, 15, 443–445.

    CAS  PubMed  Google Scholar 

  158. Killorin, W., Gray, M., Bennett, J. K., & Green, B. G. (1992). The value of urodynamics and bladder management in predicting upper urinary tract complications in male spinal cord injury patients. Paraplegia, 30, 437–441.

    CAS  PubMed  Google Scholar 

  159. Neyaz, O., Srikumar, V., Equebal, A., & Biswas, A. (2020). Change in urodynamic pattern and incidence of urinary tract infection in patients with traumatic spinal cord injury practicing clean self-intermittent catheterization. Journal Of Spinal Cord Medicine, 43, 347–352.

    PubMed  Google Scholar 

  160. Elmelund, M., Klarskov, N., Bagi, P., Oturai, P. S., & Biering-Sørensen, F. (2017). Renal deterioration after spinal cord injury is associated with length of detrusor contractions during cystometry-A study with a median of 41 years follow-up. Neurourology And Urodynamics, 36, 1607–1615.

    PubMed  Google Scholar 

  161. Gormley, E. A. (2010). Urologic complications of the neurogenic bladder. Urologic Clinics Of North America, 37, 601–607.

    PubMed  Google Scholar 

  162. Dai, G., Liu, X., Zhang, Z., et al. (2013). Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Research, 1533, 73–79.

    CAS  PubMed  Google Scholar 

  163. Mendonça, M. V., Larocca, T. F., de Freitas Souza, B. S., et al. (2014). Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury. Stem Cell Research & Therapy, 5, 126.

    Google Scholar 

  164. Muthu, S., Jeyaraman, M., Gulati, A., & Arora, A. (2021). Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: Systematic review and meta-analysis. Cytotherapy, 23, 186–197.

    PubMed  Google Scholar 

  165. Oraee-Yazdani, S., Hafizi, M., Atashi, A., et al. (2016). Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: Safety and possible outcome. Spinal Cord, 54, 102–109.

    CAS  PubMed  Google Scholar 

  166. Vaquero, J., Zurita, M., Rico, M. A., et al. (2017). Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury. Cytotherapy, 19, 349–359.

    CAS  PubMed  Google Scholar 

  167. Vaquero, J., Zurita, M., Rico, M. A., et al. (2018). Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline. Cytotherapy, 20, 806–819.

    PubMed  Google Scholar 

  168. Cheng, H., Liu, X., Hua, R., et al. (2014). Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med, 12, 253.

    PubMed  PubMed Central  Google Scholar 

  169. Yang, Y., Pang, M., Du, C., et al. (2021). Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: A phase 1/2 pilot study. Cytotherapy, 23, 57–64.

    CAS  PubMed  Google Scholar 

  170. Albu, S., Kumru, H., Coll, R., et al. (2021). Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: A randomized controlled study. Cytotherapy, 23, 146–156.

    CAS  PubMed  Google Scholar 

  171. El Zayat, A., & Badran, Y. (2018). The effect of transplantation of adipose-derived stem cells to spinal cord on the recovery of urinary bladder function in patients having spinal cord injuries: A urodynamic study. Egyptian Rheumatology and Rehabilitation, 45, 100–105.

    Google Scholar 

  172. Marks, B. K., & Goldman, H. B. (2014). Videourodynamics: Indications and technique. Urologic Clinics Of North America, 41, 383–391. vii-viii.

    PubMed  Google Scholar 

  173. Wyndaele, M., & Rosier, P. (2018). Basics of videourodynamics for adult patients with lower urinary tract dysfunction. Neurourology And Urodynamics, 37, S61–s66.

    PubMed  Google Scholar 

  174. Jiang, Y. H., Chen, S. F., & Kuo, H. C. (2020). Role of videourodynamic study in precision diagnosis and treatment for lower urinary tract dysfunction. Ci Ji Yi Xue Za Zhi, 32, 121–130.

    PubMed  Google Scholar 

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Funding

The work was supported by grants from the National Cheng Kung University Hospital (NCKUH-11206016) and Ministry of Science and Technology, Taiwan (MOST 111-2321-B-006-013).

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Authors and Affiliations

  1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701, Taiwan

    Yin-Chien Ou, Chi-Chen Huang, Pei-Chuan Ho & Kuen-Jer Tsai

  2. Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yin-Chien Ou & Yao-Lin Kao

  3. Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chi-Chen Huang

  4. Research Center of Clinical Medicine, National Cheng Kung University Hospital , College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Kuen-Jer Tsai

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Contributions

Conceptualization, K-J.T.; Data curation, Y-C.O.; Formal analysis, Y-C.O.; Investigation, Y-C.O.; Methodology, Y-C.O.; Project administration, K-J.T.; Resources, Y-C.O.; Supervision, K-J.T.; Visualization, Y-C.O., Y-L.K., and P-C.H.; Writing – original draft, Y-C.O.; Writing – review & editing, Y-C.O., C-C.H., Y-L.K., P-C.H., and K-J.T. All authors have read and agreed to the published version of the manuscript.

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Ou, YC., Huang, CC., Kao, YL. et al. Stem Cell Therapy in Spinal Cord Injury-Induced Neurogenic Lower Urinary Tract Dysfunction. Stem Cell Rev and Rep 19, 1691–1708 (2023). https://doi.org/10.1007/s12015-023-10547-9

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