Mesenchymal stem cell recruitment and improved bladder function after bladder outlet obstruction: preliminary data.
OBJECTIVE
Mesenchymal stem cells have various therapeutic benefits in various organ injury models. Bladder outlet obstruction causes smooth muscle hypertrophy and fibrosis, leading to lowered compliance, increased storage pressures and renal injury. Decreased blood flow and hypoxia may contribute to obstruction related bladder decompensation. We used a mouse model to determine whether mesenchymal stem cell recruitment occurred after bladder outlet obstruction and whether this was associated with changes in bladder hypoxia, histology and function. We also identified potential chemokines involved in mesenchymal stem cell recruitment.


METHODS
A total of 20 female mice underwent bladder outlet obstruction. Three days later 2 million green fluorescent protein labeled mesenchymal stem cells were intravenously administered. After 4 weeks urodynamic and histological evaluation was performed. Quantitative reverse transcriptase-polymerase chain reaction was done to determine relative expression of the chemokines CCL2, CCL20, CCL25, CXCL9 and CXCL16. We simultaneously studied mice with bladder outlet obstruction only without mesenchymal stem cell injection and a control group.


RESULTS
In 10 of 15 surviving mesenchymal stem cell injected mice mesenchymal stem cells were identified in the detrusor, and decreased hypoxia, hypertrophy and fibrosis was seen. Nine of 10 mice with mesenchymal stem cell engraftment had improved compliance compared to those without engraftment (mean±SD 9.6±5.1 vs 3.9±2.6 μl/cm H2O, p=0.012). Polymerase chain reaction revealed a 2-fold increase in CCL2 expression but there were no significant changes in other chemokine levels.


CONCLUSIONS
Mesenchymal stem cell recruitment to the bladder after bladder outlet obstruction appears to be associated with increased blood flow and decreased tissue hypoxia, which may contribute to improvement in histopathological and functional parameters. Mesenchymal stem cell recruitment may be related to CCL2 over expression. Additional studies in larger samples are needed but these initial results suggest a potential role for mesenchymal stem cell based therapy for bladder outlet obstruction related bladder injury.
Division of Pediatric Urology, Vanderbilt University Medical Center, Monroe Carell, Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee 37232-9820, USA.
Lynn L
LL
Woo
Stacy T
ST
Tanaka
Govindaraj
G
Anumanthan
John C
JC
Pope
John C
JC
Thomas
Mark C
MC
Adams
John W
JW
Brock
Neil A
NA
Bhowmick
D000818:Animals; D002633:Chemotaxis; D005260:Female; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction