Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction.
OBJECTIVE
Bladder outflow obstruction (BOO) is common in the elderly and can result in bladder voiding dysfunction (BVD) due to severe bladder muscle damage. The goal of this research was to evaluate the use of adult stem cells for the treatment of BVD due to decreased muscle contractility in a rat model.


METHODS
Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) were harvested from male Lewis rats and expanded in culture. BOO was induced by tying a suture around the urethra. Six weeks after obstruction, the development of BVD was confirmed by cystometric analysis in conscious rats, histology and molecular investigations. Injection of ADSCs or MPCs into the bladder wall and synchronous deligation was performed 6 weeks after the obstruction. After stem-cell treatment, morphological and functional changes were assessed. Age-matched rats and animals without cellular therapy but deligation-only served as controls.


RESULTS
Voiding pressures decreased progressively 6 weeks after obstruction with increased bladder capacities. Structural changes of the detrusor muscle occurred during the time of obstruction with an increased connective tissue-to-smooth muscle ratio and decreased SMA/smoothelin expression. After stem-cell injection, improved voiding pressures and voiding volumes were observed together with recovered tissue architecture. RT-PCR and Western blotting showed an up-regulation of important contractile proteins.


CONCLUSIONS
We established a reliable model for BVD and demonstrated that ADSCs and MPCs can prevent pathophysiological remodelling and provide regenerated bladder tissue and function.
Division of Urology, University Hospital Zürich (USZ), 8091, Zurich, Switzerland.
Mathias
M
Tremp
Souzan
S
Salemi
Remo
R
Largo
Karl-Erik
KE
Andersson
Jan A
JA
Plock
Jan
J
Plock
Tamer
T
Aboushwareb
Tullio
T
Sulser
Daniel
D
Eberli
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D032446:Myoblasts / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013234:Stem Cells; D001748:Urinary Bladder Neck Obstruction / Q000601:surgery*