A non-invasive method to evaluate the efficacy of human myoblast in botulinum-A toxin induced stress urinary incontinence model in rats.
OBJECTIVE
To develop a simple non-invasive method to assess the efficacy of a cell based therapy for treating stress urinary incontinence (SUI).


METHODS
In this study, skeletal myoblasts were used as candidate therapy to reverse SUI. The SUI model was created in rats using periurethral injection of botulinum-A toxin injection. Two weeks later, the rats were administered saline and the level of continence in each botulinum-A toxin treated and control animals was assessed by the extent of voiding using metabolic cages. To determine the efficacy of myoblasts to reverse SUI, botulinum-A toxin treated incontinent rats were injected with either cultured human skeletal myoblasts or with buffered saline (sham control). Two weeks post implantation, the extent of continence was evaluated as mentioned above.


RESULTS
The difference in void volume between botulinum-A toxin -treated and control rats were significant. Histological analysis of the urethra showed remarkable atrophy of the muscular layer. A significant reversal (P = .025) in the volume of voiding was observed in cell-implanted rats as compared to sham injected rats. Histological analysis of the urethra implanted with myoblasts showed recovery of the atrophied muscular layer in comparison to sham control. Immunofluorescence analysis of the cell injected tissues confirmed the presence of human myoblasts in the regenerated area.


CONCLUSIONS
This simplified method of in vivo testing can serve as a tool to test the efficacy of new therapies for treating SUI.
Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. Ltd., DALC Campus,Navi Mumbai 400701, India.
Balaji
B
Bandyopadhyay
Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. Ltd., DALC Campus,Navi Mumbai 400701, India.
Anirban
A
Thakur
Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. Ltd., DALC Campus,Navi Mumbai 400701, India.
Viral
V
Dave
Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. Ltd., DALC Campus,Navi Mumbai 400701, India.
Chandra
C
Viswanathan
Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. deepa.ghosh@relbio.com.
Deepa
D
Ghosh
D000818:Animals; D019274:Botulinum Toxins, Type A; D004195:Disease Models, Animal; D006801:Humans; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014521:Urethra / Q000473:pathology*; D014550:Urinary Incontinence, Stress / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D014554:Urination
D019274:Botulinum Toxins, Type A