Bladder outlet obstruction (BOO) caused by
collagen deposit is one of the most common problems in elderly male. This study was performed to examine the capability of human mesenchymal stem cells (MSCs) overexpressing
hepatocyte growth factor (HGF) to inhibit
collagen deposition in rat model of
bladder outlet obstruction (BOO). HGF is known for its antifibrotic effect and the most promising agent for treating bladder
fibrosis. BM3.B10 stable immortalized human MSC line (B10) was transduced to encode human HGF with a retroviral vector was prepared (B10.HGF). Two weeks after the onset of BOO, B10, and B10.HGF cells were injected into the rat's bladder wall. After 4 weeks, bladder tissues were harvested and Masson's trichrome staining was performed. Transgene expression in HGF-expressing B10 cells was demonstrated by
reverse transcriptase polymerase chain reaction and immunohistochemical staining, and the high levels of HGF secreted by B10.HGF cells was confirmed by ELISA. The mean bladder weight in BOO rats was 5.8 times of the normal controls, while in animals grafted with B10.HGF cells, the weight was down to four times of the control [90.2 ± 1.6 (control), 89.9 ± 2.8 (
sham), 527.9 ± 150.9 (BOO), 447.7 ± 41.0 (BOO + B10), and 362.7 ± 113.2 (BOO + B10.HGF)]. The mean percentage of
collagen area increased in BOO rats, while in the animals transplanted with B10.HGF cells, the
collagen area decreased to the normal control level [12.2 ± 1.3, (control), 12.8 ± 1.1 (
sham), 26.6 ± 2.7 (BOO), 19.9 ± 6.0 (BOO + B10), and 13.3 ± 2.1 (BOO + B10.HGF)]. The expression of
collagen and TGF-b
protein increased after BOO, while the expression of HGF and c-met
protein increased in the group with B10.HGF
transplantation after BOO. Intercontraction interval decreased after BOO, but it recovered after B10.HGF
transplantation. Maximal voiding pressure (MVP) increased after BOO, and it recovered to levels of the normal control after
transplantation of B10.HGF cells. Residual urine volume (RU) increased after BOO, but the RU increase was not reversed by
transplantation of B10.HGF cells. Human MSCs overexpressing HGF inhibited
collagen deposition and improved cystometric parameters in
bladder outlet obstruction of rats. The present study indicates that
transplantation of MSCs modified to overexpress HGF could serve as a novel therapeutic strategy against bladder
fibrosis in patients with
bladder outlet obstruction.