Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model.
BACKGROUND
Stem cell therapy is a promising therapeutic strategy for stress urinary incontinence (SUI). However, its current efficacy is insufficient.


OBJECTIVE
We designed a stem cell transplantation system that contains autologous adipose-derived stem cells (ADSC) and controlled-release nerve growth factor (NGF). We evaluated whether this system could enhance the therapeutic efficacy of ADSCs by periurethral coinjection in SUI rats.


METHODS
We first tested for the presence of NGF receptors in rat ADSCs and observed the effect of NGF on ADSCs in vitro and in vivo. NGF was encapsulated within poly(lactic-co-glycolic acid-PLGA) microspheres (PLGA/NGF) to control its release. SUI was created in rats, and ADSCs were harvested, cultured from fat tissue, and retained for later transplantation. SUI rats then received different forms of periurethral injection therapy. Their urodynamic index was monitored. Eight weeks after injection, the SUI rats were sacrificed and their urethra removed for histologic evaluation.


METHODS
Forty SUI rats were allocated to five groups for receiving periurethral injection with phosphate-buffered saline (PBS), ADSC, ADSC+PLGA, ADSC+NGF, or ADSC+PLGA/NGF. Bladder capacities, abdominal leak point pressure (ALPP), and retrograde urethral perfusion pressure (RUPP) were reassessed at 2, 6, and 8 wk after injection.


METHODS
The rat SUI model was generated by bilateral pudendal nerve transection (PNT). Real-time polymerase chain reaction (RT-PCR) and western blotting detected the NGF receptor Ark-A. The regeneration of muscles and peripheral nerves was evaluated by Masson's trichrome and immunohistochemical staining.


CONCLUSIONS
Results revealed the presence of the NGF receptor Trk-A on rat ADSCs. Short-term observations showed that NGF could improve ADSCs' viability in vitro and in vivo. ADSCs delivered intramuscularly into the urethra in combination with PLGA/NGF resulted in significant improvements in ALPP and RUPP as well as the amount of muscle and ganglia. There was a significant difference between the ADSC+PLGA/NGF group and other groups.


CONCLUSIONS
Periurethral coinjection of autologous ADSCs with controlled-release NGF may be a potential strategy for SUI treatment.
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Weiming
W
Zhao
Cheng
C
Zhang
Chengjun
C
Jin
Zijian
Z
Zhang
Deling
D
Kong
Wanhai
W
Xu
Youcheng
Y
Xiu
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014182:Transplantation, Autologous; D014521:Urethra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D014550:Urinary Incontinence, Stress / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014563:Urodynamics / Q000187:drug effects
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA