Stem Cell Therapy for Neurogenic Bladder Dysfunction in Rodent Models: A Systematic Review

Abstract

Purpose: Neurogenic bladder dysfunction (NGB) has an impact on the quality of life, which made it an important research subject in preclinical studies. The present review investigates the effect of stem cell (SC) therapy on bladder functional recovery after the onset of spinal cord injury (SCI), multiple sclerosis (MS), Parkinson disease (PD), and stroke in rodent models.

Methods: All experiments evaluated the regenerative potential of SC on the management of NGB in rodent models up to June 2019, were included. From 1,189 relevant publications, 20 studies met our inclusion criteria of which 15 were conducted on SCI, 2 on PD, 2 on stroke, and 1 on MS in the rodent models. We conducted a meta-analysis on SCI experiments and for other neurological diseases, detailed urodynamic findings were reported.

Results: The common SC sources used for therapeutical purposes were neural progenitor cells, bone marrow mesenchymal SCs, human amniotic fluid SCs, and human umbilical cord blood SCs. There was a significant improvement of micturition pressure in both contusion and transaction SCI models 4 and 8 weeks post-SC transplantation. Residual urine volume, micturition volume, and bladder capacity were improved 28 days after SC transplantation only in the transaction model of SCI. Nonvoiding contraction recovered only in 56 days post-cell transplantation in the contusion model.

Conclusion: Partial bladder recovery has been evident after SC therapy in SCI models. Due to limitations in the number of studies in other neurological diseases, additional studies are necessary to confirm the detailed mechanism for bladder recovery.

Keywords: Neurogenic bladder; Rodent models; Stem cell therapy; Systematic review.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of included studies in qualitative and quantitative stages. SCI, spinal cord injury; PD, Parkinson disease; MS, multiple sclerosis.

Fig. 2.

Percentage of selected experiments for each item in the modified version of the CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) quality checklist.

Fig. 3.

Micturition pressure improvement based on spinal cord injury type. CI, confidence interval.

Fig. 4.

Micturition pressure improvement based on the time of urodynamics assessment. CI, confidence interval.

Fig. 5.

Residual urine volume improvement based on spinal cord injury type. CI, confidence interval.

Fig. 6.

Residual urine volume improvement based on the time of urodynamics assessment. CI, confidence interval.

Fig. 7.

Nonvoiding contraction improvement based on spinal cord injury type and the time of urodynamics assessment. CI, confidence interval.

Fig. 8.

Bladder capacity improvement based on spinal cord injury type. CI, confidence interval.

Fig. 9.

Bladder capacity improvement based on the time of urodynamics assessment. CI, confidence interval.

Fig. 10.

Micturition volume improvement based on spinal cord injury type and the time of urodynamics assessment. CI, confidence interval.

Fig. 11.

Funnel plot of standard error by the standard difference in means.