Generation of induced human Schwann cells
Research type
Research Study
Full title
Generation of induced human Schwann cells for in vitro and in vivo study of nerve repair and neuropathy
IRAS ID
289886
Contact name
Peter Arthur-Farraj
Contact email
Sponsor organisation
University of Cambridge
Duration of Study in the UK
10 years, 0 months, 1 days
Research summary
Disorders of peripheral nerves are common and a significant number of trauma victims have injuries to peripheral nerves that require surgical intervention. Unfortunately, human nerve regeneration is inefficient and less than 50% of patients regain adequate function after surgical repair and this worsens with increasing age and a more proximal location of injury (increasing the regeneration distance).
A key determinate of the success of nerve regeneration from studies in mammals and fish is the activation of a large set of genes, termed the repair program, after an injury, by the nerve supporting cells, Schwann cells. Schwann cells strongly promote the survival and regeneration of the severed projections (axons) of nerve cells back to their original target. Schwann cells, only support regeneration for a period of time after injury before they become inactive and die. Unfortunately, this is often long before the regenerative process has been completed. While nerve grafts and transplanted cultured human Schwann cells offer partial strategies to improve outcomes from nerve injuries they are limited by availability of nervous system tissue.
This project proposes to develop an efficient procedure to generate Schwann cells from human skin cells (fibroblasts) without the use of viruses. Skin biopsies have been obtained from healthy controls as part of the linked project (REC09/H0311/88). These have been cultured to provide a supply of fibroblasts. This would provide an abundant personalised source of Schwann cells for transplantation for people with peripheral nerve injuries in addition to acquired neuropathies.
To demonstrate repair and remyelination potential, this study will also aim to graft induced Schwann cells into rodent models of peripheral nerve injury. Furthermore, this project will also afford the opportunity to study central molecular pathways for normal peripheral nerve function in human cells through genetic and biochemical interrogation, including transcriptomics.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
21/WM/0216
Date of REC Opinion
24 Aug 2021
REC opinion
Favourable Opinion