Stem Cell-Based Approaches to Improve Nerve Regeneration: Potential Implications for Reconstructive Transplantation?

Abstract

Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cell-based therapies have been postulated and tested in pre-clinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues for regenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patient-specific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across "gaps" in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration.

Adipose-Derived Stem Cells as a Tool in Cell-Based Therapies

“…Some studies confirm their differentiation into neuronal cells, both morphologically and functionally (Seo et al 2005). Many researchers see hope in treatment of nerve injuries using ASCs thus, confirming their participation in neuronal regeneration (Mizuno et al 2012; Khalifian et al 2015; Zack-Williams et al 2015). …”

Supercritical Carbon Dioxide-decellularized Porcine Acellular Dermal Matrix combined with Autologous Adipose-derived Stem Cells: Its Role in Accelerated Diabetic Wound Healing

“…Adipose-derived stem cells (ASCs) are ideal pluripotent cells for producing various types of tissues through tissue engineering for clinical application [11]. For instance, autologous ASCs and their clinical efficacy and safety in tissue regeneration have been investigated from breast reconstruction to neural regeneration in the spinal cord [12][13][14]. Autologous ASCs accelerate wound healing in the treatment of chronic ulcers of lower extremities in peripheral artery disease, which is closely associated with DM [15].…”

Exploring cell-based tolerance strategies for hand and face transplantation

“…Multiple studies in animal models have demonstrated the ability of MSCs to facilitate peripheral nerve regeneration through differentiation into and interaction with SC [175][176][177][178][179]. Local administration of adipose-derived MSCs in a mouse model of a crush nerve injury demonstrated improved recovery of motor and sensory function [180], and recovery of motor function was also improved by MSC treatment in a rat model of nerve transection [176].…”