Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence.
OBJECTIVE
We explored the use of autologous muscle derived cells as a method of treating stress urinary incontinence. We determined whether urethral muscle derived cell injection is feasible and compared it with bovine collagen injection.


METHODS
Muscle derived cells isolated from female Sprague-Dawley rats were first transduced with retrovirus carrying the transgene for beta-galactosidase. We injected approximately 1 to 1.5 x 106 cells into the bladder wall and proximal urethra of 6 autologous animals. Tissue was harvested after 3 and 30 days, sectioned, stained for fast myosin heavy chain and assayed for beta-galactosidase. To compare muscle derived cell and bovine collagen injections 100 microl. of commercially available bovine collagen were also injected in Sprague-Dawley female rats. Tissue was harvested in 3 animals each after 3 and 30 days, sectioned and stained for trichrome. Subsequently, 3 adult SCID mice were used to compare the level of transgene expression at each time point after injecting 1.5 x 106 cells per injection, which were transduced with adenovirus carrying the transgene for beta-galactosidase.


RESULTS
A large number of cells expressing beta-galactosidase were observed in the bladder and urethral wall 3 and 30 days after autologous cell injection in Sprague-Dawley rats. The persistence of primary muscle derived cells at 3 days was similar to that of collagen. However, at 30 days there was significant cell persistence while only a minimal amount of injected bovine collagen was detectable. Approximately 88% of the beta-galactosidase expression at day 3 remained at day 30 in SCID mice.


CONCLUSIONS
We present 2 new findings important for the emerging field of urological tissue engineering, including the feasibility of injecting autologous skeletal muscle derived cells into the lower urinary tract and the greater persistence of such injected cells versus injected bovine collagen. Therefore, autologous muscle derived cell injection may be an attractive alternative treatment option for stress urinary incontinence.
Yokoyama
T
T
Departments of Urology, Pharmacology, Orthopedic Surgery and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Yoshimura
N
N
Dhir
R
R
Qu
Z
Z
Fraser
M O
MO
Kumon
H
H
de Groat
W C
WC
Huard
J
J
Chancellor
M B
MB
D000818:Animals; D002417:Cattle; D002470:Cell Survival; D017690:Cell Transplantation; D003094:Collagen / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D051379:Mice; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019076:Transgenes; D014182:Transplantation, Autologous; D014521:Urethra / Q000166:cytology; D001743:Urinary Bladder / Q000166:cytology; D014550:Urinary Incontinence, Stress / Q000517:prevention & control*; D001616:beta-Galactosidase / Q000235:genetics
D003094:Collagen; D001616:beta-Galactosidase