title: Combined effects of brain-derived neurotrophic factor immobilized poly-lactic-co-glycolic acid membrane with human adipose-derived stem cells and basic fibroblast growth factor hydrogel on recovery of erectile dysfunction.
abstract: Erectile dysfunction (ED) is the most frequent long-term problem after radical prostatectomy. We aimed to evaluate whether the use of combination therapy with basic fibroblast growth factor (bFGF)-hydrogel on corpus cavernosum and with adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)-immobilized poly-lactic-co-glycolic acid (PLGA) membrane on the cavernous nerve (CN) could improve erectile function in a rat model of bilateral cavernous nerve crush injury (BCNI). Rats were randomly divided into five groups (n=15 per group): a normal group (N group), a group receiving saline application after bilateral cavernous nerve crush injury (BCNI), a group undergoing bFGF-hydrogel injection in the corpus cavernosum after BCNI (bFGF), a group receiving ADSC application covered with BDNF-membrane after BCNI (ADSC/BDNF), and a group undergoing coadministration of bFGF-hydrogel injection and BDNF-membrane with ADSCs after BDNF (bFGF+ADSC/BDNF). Four weeks postoperatively, the erectile function was assessed by detecting the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP). Smooth muscle and collagen contents were measured using Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. The protein expression of the α-smooth muscle actin (α-SMA) and the cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by western blot and cGMP assay, respectively. In the bFGF+ADSC/BDNF group, the erectile function was significantly elevated compared with the BCNI and other treated groups and showed a significantly increased smooth muscle/collagen ratio, nNOS content, α-SMA expression, and cGMP level. In particular, there were no statistical differences in the ICP/MAP ratio, smooth muscle/collagen ratio, and α-SMA and cGMP levels between the bFGF+ADSC/BDNF group and normal group. Application of the BDNF-immobilized PLGA membrane with human ADSC into the CN and bFGF-incorporated hydrogel into the corpus carvernosum improved nearly normal erectile function in a rat model of postprostatectomy ED. This result suggests that a combined application of bFGF+ADSC/BDNF might be a promising treatment for postprostatectomy ED.
authors.affiliation: 1 Department of Urology, Gangnam Severance Hospital, Yousei University Health System , Seoul, Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: In Gul
authors.initials: IG
authors.lastname: Kim
authors.forename: Ae Ryang
authors.initials: AR
authors.lastname: Jung
authors.forename: Kshitiz Raj
authors.initials: KR
authors.lastname: Shrestha
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Dong
authors.initials: KD
authors.lastname: Park
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Chung
authors.forename: Sae Woong
authors.initials: SW
authors.lastname: Kim
authors.forename: Ki Hean
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji Youl
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000138:chemical synthesis; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000209:etiology / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000628:therapy*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004337:Drug Carriers; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid