In vitro study of decellularized rat tissues for nerve regeneration

Abstract

Peripheral nerve injuries cause an absence or destruction of nerves. Decellularized nerves, acting as a replacement for autografts, have been investigated in the promotion of nerve repair and regeneration, always being incorporated with stem cells or growth factors. However, such a strategy is limited by size availability. The potential application in heterotopic transplantation of other decellularized tissues needs to be further explored. In this study, rat decellularized kidney (dK) was selected to be compared with decellularized peripheral nerve (dN), since dK has aboundant ECM components and growth factors. The PC-12 cells were cultured on dK and dN scaffolds, as shown in the similar behaviors of cell metabolism and viability, but have a more regular arrangement on dN compared to dK, indicating that the natural structure plays an important role in guiding cell extension. However, we found significant upregulation of axon–growth–associated genes and proteins of PC-12 cells in the dK group compared to the dN group by qRT-PCR, immunofluorescence, and western blotting. Furthermore, various neurotrophic factors and growth factors of acellular kidney and nerve were evaluated by ELISA assay. The lower expression of neurotrophic factors but higher expression of growth factors such as VEGF and HGF from dK suggests that axon growth and extension for PC-12 cells may be partially mediated by VEGF and HGF expression from decellularized kidney, which further points to a potential application in nerve repair and regeneration.

A grooved conduit combined with decellularized tissues for peripheral nerve regeneration

“…DK was chosen in this study to compare with DN due the enrichment of erythropoietin (EPO) that could promote the regeneration in optic nerve [ 24 ] and peripheral nerve [ 25 ], which could explain why DK + GC performed better than GC alone in electrophysiological detection, gastrocnemius proportion measurement, and histological assessments. However, based on our previous study [ 47 ], DK had much lower expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 1 (FGF1) compared with DN. All these growth factors have critical influence on the promotion of nerve cell migration, proliferation, survival, outgrowth of sensory, sympathetic, and motor nerve regeneration [ 48 – 50 ], which could have a better promotion effect on nerve regeneration compared with EPO and lead to the better performance of GC + DN compared with GC + DK.…”