Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury.
BACKGROUND
Cavernous nerve injury is the main reason for post-prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED.


OBJECTIVE
To evaluate the therapeutic efficacy of adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF) immobilized Poly-Lactic-Co-Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post-prostatectomy ED. Methods.  Rats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF-membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF-membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled-released for a period of 4 weeks in a BDNF/PLGA porous membrane system.


METHODS
Four weeks after the operation, erectile function was assessed by detecting the ratio of intra-cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho-endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively.


RESULTS
In the ADSC/BDNF-membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF-membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups.


CONCLUSIONS
ADSCs with BDNF-membrane on the cavernous nerve can improve erectile function in a rat model of post-prostatectomy ED, which may be used as a novel therapy for post-prostatectomy ED.
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Shuyu
S
Piao
In Gul
IG
Kim
Ji Young
JY
Lee
Sung Hoo
SH
Hong
Sae Woong
SW
Kim
Tae-Kon
TK
Hwang
Se Heang
SH
Oh
Jin Ho
JH
Lee
Jeong Chan
JC
Ra
Ji Youl
JY
Lee
D017667:Adipocytes / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D006152:Cyclic GMP / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D055767:Immobilized Proteins / Q000008:administration & dosage*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008567:Membranes, Artificial; D009409:Nerve Crush / Q000379:methods; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010413:Penis / Q000294:innervation / Q000601:surgery; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011468:Prostatectomy / Q000009:adverse effects; D060525:Pudendal Nerve / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*
D019208:Brain-Derived Neurotrophic Factor; D055767:Immobilized Proteins; D008567:Membranes, Artificial; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP