Recovery of erectile function comparing autologous nerve grafts, unseeded conduits, Schwann cell seeded guidance tubes and GDNF-overexpressing Schwann cell grafts

Abstract

Dissection of the cavernous nerves during radical prostatectomy for prostate cancer eliminates spontaneous erections. Using the rat as an experimental model, we compared the regenerative capacity of autologous nerve grafts and Schwann-cell-seeded nerve guides. After bilateral excision of cavernous nerve segments, cavernous nerves were reconstructed using unseeded silicon tubes, nerve autografts and silicon tubes seeded with either Glial-cell-line-derived (GDNF)-overexpressing or green fluorescent protein (GFP)-expressing Schwann cells (SCs) (16 study nerves per group). Control groups underwent either a sham operation or bilateral excision of cavernous nerve segments without repair. After 12 weeks erectile function was assessed by neurostimulation and intracavernous pressure (ICP) measurement. The reconstructed nerve segments were excised and histologically analyzed. We demonstrated an intact erectile response upon neurostimulation in 25% (4/16) of autologous nerve grafts, in 50% (8/16) of unseeded tubes, in 75% (12/16) of the Schwann-cell–GFP group and in 93.75% (15/16) of the GDNF group. ICP was significantly increased when comparing the Schwann-cell–GFP group with nerve autografts, unseeded conduits and negative controls (P<0.005). In conclusion, Schwann-cell-seeded scaffolds combined with neurotrophic factors are superior to unseeded tubes and autologous nerve grafts. They present a promising therapeutic approach for the repair of erectile nerve gaps.

Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction

“…The pre-clinical studies have shown significant improvement in terms of restoring erectile functions through cell-based therapies in ED animal models, which could be improved through LI-ESWT by increasing cell viability, proliferation, and multilineage differentiation [144]. A recent study showed an improved therapeutic efficacy of Schwann cells with overexpressing GDNF in CNI-induced ED rats [145]. Thus, the overexpression of relevant growth factors may be targeted to promote rapid stem cell-mediated regeneration of damaged cavernosal nerves.…”

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

“…Autografts demonstrate considerable recovery results, especially in long-gap injuries (>3 cm) [ 39 , 40 ]. However, several limitations are associated with the implementation of autografts, including scarcity of the tissue source, second surgery trauma, donor-site function loss and morbidity, and mismatches in tissue size [ 8 ]. An allograft from a cadaver or donor is an alternative option.…”

“…The current clinical standard for long-gap PNI repair is using autografts [ 7 ]. However, this is often limited by size mismatch, source shortage, and permanent damage to the donor site [ 8 ]. Distinct from the PNS, the spinal cord has poor regenerative capacity, and, currently, there are still no effective clinical treatments for SCI [ 9 ].…”

Materials for peripheral nerve repair constructs: Natural proteins or synthetic polymers?

“…A silicone tube seeded with Schwann cells modified to overexpress GDNF was assessed in a 5 mm rat cavernous nerve defect model (May et al, 2016). At 12 weeks, erectile function was restored in significantly more rats that received the experimental conduit than received an autograft (May et al, 2016).…”

“…A silicone tube seeded with Schwann cells modified to overexpress GDNF was assessed in a 5 mm rat cavernous nerve defect model (May et al, 2016). At 12 weeks, erectile function was restored in significantly more rats that received the experimental conduit than received an autograft (May et al, 2016). However, function was also restored in twice as many rats that underwent repair using an empty tube compared to autograft repair (May et al, 2016).…”