Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction.
OBJECTIVE
Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model.


METHODS
We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting.


RESULTS
Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells.


CONCLUSIONS
Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy.
Tanaka
Stacy T
ST
Division of Pediatric Urology, Monroe Carell, Jr. Vanderbilt Children's Hospital, Nashville, Tennessee 37232-9820, USA. stacy.tanaka@vanderbilt.edu
Martinez-Ferrer
Magaly
M
Makari
John H
JH
Wills
Marcia L
ML
Thomas
John C
JC
Adams
Mark C
MC
Brock
John W
JW
Pope
John C
JC
Bhowmick
Neil A
NA
D000818:Animals; D001854:Bone Marrow Cells; D005260:Female; D005355:Fibrosis; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology*