The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair

Abstract

Combinations of fibroblasts (Fbs) and corresponding epithelial cells have been widely used in many tissues, such as the skin and breast tissues, to augment tissue repair and remodeling. Recently, a large amount of new data has indicated that nerve Fbs play critical roles in Schwann cells (SCs) and axons in vitro. However, little is known regarding the effects of co-transplanting nerve Fbs and SCs on peripheral nerve repair in vivo. The aim of this study was to investigate the effect of co-transplanting sciatic nerve Fbs (SN-Fbs) and sciatic nerve SCs (SN-SCs) on nerve regeneration. We developed a 5 mm nerve-defect model in mice using a polyurethane (PUR) catheter and then injected one of four different mixtures of cells into the catheters to form the following four groups: pure Matrigel (Control group), SN-Fbs alone (SN-Fb group), SN-Fbs combined with SN-SCs at a ratio of 1:2 (Fb&SC group) and SN-SCs alone (SN-SC group). Histological and functional analyses were performed 3 months later. The results indicated that in vitro, the expression levels of NGF, BDNF and GDNF were significantly higher, and in vivo, a more moderate amount of extracellular matrix was produced in the Fb&SC group than in the SN-SC group. Compared to the other groups, co-transplanting SN-Fbs with SCs at a 1:2 ratio had significantly positive effects on nerve regeneration and functional recovery.

Development of a Piezoelectric PVDF‐TrFE Fibrous Scaffold to Guide Cell Adhesion, Proliferation, and Alignment

“…[76] Further, they help facilitate the sorting of Schwann cells during regeneration and promote the secretion of collagen, basal lamina, brain derived neurotrophic factor, and glial derived neurotrophic factor, post-injury. [19] Our analysis simultaneously confirmed the biocompatibility of Schwann cells and fibroblasts while introducing unique characterization methods to assess phenotype response. Using adhesion as a marker for viability, penetration as a marker for in vivo applicability, and alignment as a marker for regenerative response, we have quantitatively detailed the biological response to changes in physical characteristics, crystalline structure, and piezoelectricity of PVDF-TrFE scaffolds.…”

“…Schwann cells and fibroblasts were utilized to emulate a regenerative PNS environment due to the interplay between the two cell types post-injury. [19,27,73,74] Schwann cells differentiate into a progenitor phenotype following traumatic injuries in order to secrete extracellular matrix proteins. [75] Fibroblasts, like Schwann cells, also play a critical role in PNS regeneration.…”

“…[75] Fibroblasts, like Schwann cells, also play a critical role in PNS regeneration. [19,27,73,74,[76][77][78] First, they are a primary source of fibronectin, an ECM protein crucial to the formation of Bands of Büngner. [76] Further, they help facilitate the sorting of Schwann cells during regeneration and promote the secretion of collagen, basal lamina, brain derived neurotrophic factor, and glial derived neurotrophic factor, post-injury.…”

“…[16,17] Though scarce in total, in vivo models have utilized PVDF-TrFE as nerve conduits to enhance regeneration of axons, ancillary cells, and neurotrophic factors such as astrocyte processes and blood vessels. [18,19] The tunable physical, chemical, and electrical properties of PVDF-TrFE make fabricated scaffolds an ideal template for PNS biomaterials. Specifically, the piezoelectric capacity of the fibers complements the distinct electrical environment characterizing the nervous system.…”

“…[23][24][25][26][27] Likewise, fibroblasts have been identified as crucial supportive cells that promote the alignment and migration of Schwann cells while simultaneously depositing additional ECM proteins and neurotrophic factors. [19,26] Therefore, this work aims to create tunable PVDF-TrFE scaffolds with extensive characterization of the parameters beneficial to a regenerative neurotrophic environment. Uniquely, Schwann cells and fibroblast cells were used to determine the morphological cell response to varied electrospinning parameters through quantified measurements including cell alignment, elongation, and viability.…”