Effects of intracavernous injection of adipose-derived stem cells on cavernous nerve regeneration in a rat model

Abstract

The aim of this study was to investigate effects of intracavernous injection of adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Thirty Sprague-Dawley male rats were randomly divided into three equal groups: one group underwent sham operation, while two groups underwent bilateral CN crush. Crush-injury group was treated at the time of injury with intracavernous injection of ADSCs, or injured control group with no further intervention. Erectile function was assessed by CN electrostimulation after 3 months. Penile tissue and crushed nerves were collected for histology. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate intracavernous injection of ADSCs, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the intracavernous injection of ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibers than the injured control group but fewer than the sham group. Intracavernous injection of ADSCs treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. These results show that the intracavernous injection of ADSCs to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that penile injection of ADSCs can improve recovery of erectile function in a rat model of neurogenic ED.

Fig. 1

Major pelvic ganglion and cavernous nerve of a rat under a surgical microscope (×100)

Fig. 2

Electrostimulation of CNs after 3 months. a Group A the sham-operated group. b Group B the injured control group. c Group C the ADSCs treated group. d The ICP/MAP ratio was compared among the three groups of rats. *P < 0.05, compared with group B; **P < 0.05, compared with group A

Fig. 3

Toluidine blue staining of CNs. a Group A there were abundant myelinated axons of CNs that had a normal morphological appearance. b Group B the number of myelinated axons decreased substantially and displayed the phenomenon of atrophy. c Group C there was a significant increase in the regeneration of well-orientated myelinated axons relative to group B ×1000. d Myelinated axons. *P < 0.05, compared with group B; **P < 0.05, compared with group A

Fig. 4

NADPH-diaphorase staining of dorsal nerves. a Group A there was predominant blue staining of nerve fibers. b Group B there was a paucity of blue-stained fibers. c Group C there was a significant increase in the number of blue-stained nerve fibers relative to group B ×400. d NADPH-diaphorase-positive nerve fibers. *P < 0.05, compared with group B; **P < 0.05, compared with group A (Color figure online)

Fig. 5

Masson’s trichrome staining in a penile midshaft specimen. Representative images of the corpus cavernosum in each cohort. a Sham-operated group. b Injured control group. c ADSCs treated group, original magnification ×100. d The graph depicts the ratio of smooth muscle-to-collagen in penile midshaft sections. *P < 0.05

Fig. 6

a The expression of nNOS at 3 months after cavernosal nerve injury. b The graph showing protein levels as relative expression as compared with β-actin. *P < 0.05, compared with group B; **P < 0.05, compared with group A