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.

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

“…bFGF is a member of the fibroblast growth factor family, which plays a significant role in the pathogenesis of several diseases including osteogenesis, adipogenesis, and normal wound healing, by inducing angiogenesis (Tabata, ). It was reported that bFGF treatment ameliorated erectile function in animal models (Suetomi et al ., ; Bae et al ., ; Lee et al ., ). Takahiro et al .…”

Essential role of brain-derived neurotrophic factor (bdnf) in diabetic erectile dysfunction

“…The cavernosal nerve is distributed in the cavernous body of the urethra, corpus cavernosum and erectile tissue and is formed by the sympathetic nerve, which is the main nerve that regulates penile erection. It has been confirmed that neuropathy plays a major role in the pathophysiology of diabetic ED (Hecht, Neundorfer, Kiesewetter, & Hilz, ; Lee et al., ).…”

Transplanted Adipose‐Derived Stem Cells Ameliorate Testicular Dysfunction In A D‐Galactose–Induced Aging Rat Model

“…The inherent deficiency of SOD2, a potent component of the SOD family, in testicular tissues also contributes to the vulnerability of this tissue to D‐gal—induced oxidative stress. The antioxidant effects of ADSCs have been described previously (Lee et al, ). In our study, treatment with ADSCs alleviated the D‐gal—induced alteration in testicular oxidant balance.…”