Developing an In Vitro Model to Screen Drugs for Nerve Regeneration

Abstract

Peripheral nerve injuries (PNI) have a high prevalence and can be debilitating, resulting in life‐long loss or disturbance in end‐organ function, which compromises quality of life for patients. Current therapies use microsurgical approaches but there is the potential for enhancing recovery through other therapeutic modalities such as; cell‐based conduits, gene therapy and small molecules. A number of molecular targets and drugs which have the potential to improve nerve regeneration have been identified, however, there are challenges associated with moving therapies toward clinical translation. Due to the lack of detailed knowledge about the pro‐regenerative effect of potential drug treatments, there is a need for effective in vitro models to screen compounds to inform future pre‐clinical and clinical studies. The interaction between regenerating neurites and supporting Schwann cells is a key feature of the nerve environment, therefore, in vitro models that mimic this cellular association are useful tools. In this study, we have investigated various cell culture models, including simple monolayer systems and more complex 3D‐engineered co‐cultures, as models for use in PNI drug development. Anat Rec, 301:1628–1637, 2018. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Tissue Engineered Bands of Büngner for Accelerated Motor and Sensory Axonal Outgrowth

“…In addition to their therapeutic potential, TE-BoBs could also serve as an in vitro testbed for rapid, high throughput screening of mechanisms and efficacy of pro-regenerative strategies in a physiologically-relevant, 3D model of nerve regeneration. There is a growing demand across all science disciplines for tissue engineered 3D models which more closely mimic complex in vivo mechanisms, ultimately increasing translatable drug discovery and reducing the need for in vivo animal models (Nam et al, 2015;Vanderburgh et al, 2017;Rayner et al, 2018). Thus, the structural and phenotypical similarities between TE-BoBs and natural bands of Büngner suggest potential for future applications which require an anatomically-and physiologically-inspired proregenerative testing environment in vitro.…”

Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?

“…[246][247][248] Small molecules like fusicoccin-A, tegaserod, 5-(nonyloxy)tryptamine and vinorelbine enhanced nerve repair in vivo. [249][250][251][252] Bioactive Peptides: Bioactive peptides that possess the active motifs of proteins are more cost-effective than growth factors for incorporation into scaffolds. These natural/synthetic short peptide sequences can activate cell surface receptors for growth factors and regulate the corresponding signals.…”

“…[ 246–248 ] Small molecules like fusicoccin‐A, tegaserod, 5‐(nonyloxy)tryptamine and vinorelbine enhanced nerve repair in vivo. [ 249–252 ]…”

Advances in the Ongoing Battle against the Consequences of Peripheral Nerve Injuries

“…These drug features must be adequately tested on a new generation of models to screen nerve regeneration pharmacological therapies. In this Thematic Papers issue, Rayner et al, () have used 3D engineered neural tissue co‐cultures, compared to PC12, NG108–15, or dorsal root ganglion monolayers, in order to develop a model able to mimic the interaction between regenerating neurites and supporting Schwann cells. 3D engineered neural tissue is an anisotropic cellular hydrogel used to seed with Schwann or Schwann‐like cells (O'Rourke et al, ).…”