Michael Fehlings, University of Toronto, Canada, USA

Investigation of human piggyBac induced pluripotent stem cells for repair and regeneration of the injured cervical spinal cord

Funded in: 2011, 2012, 2013, 2014, 2015

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The spinal cord is rarely transected even after severe trauma, and most injuries are characterized by a surviving thin rim of axons at the site of injury. Preserve this surviving tissue and significantly improve outcomes following SCI is one aim of clinical interventions.

Oligodendrocytes are particularly susceptible to apoptosis following SCI contributing to progressive myelin loss. Previous studies found that transplants of NPCs (neural precursor cells) can remyelinate spinal cord axons and enhance locomotor recovery after SCI. In the literature it is suggested that remyelination of the surviving axons is the main beneficial outcome in cell replacement therapies for SCI.

This study will examine the ability of iPS-dervied oligodendrocytes to promote functional recovery in a rodent model of cervical SCI.

The team has recently engineered a unique, non-viral method of reprogramming fibroblasts into induced pluripotent stem (iPS) cells. Our piggyBac (PB) transposition reprogramming technique allows for the seamless excision of the transgenes following the induction of pluripotency, thereby removing their potential mutagenic nature.

This novel PB-reprogramming technique offers the possibility of xeno-free production of patientspecific autogenous stem cells, therefore attenuating the potentially deleterious effects of a host immune response. Based on exciting proof of concept data that non-viral iPS cells can be transformed into adult-type NPC and can be successfully used to remediate the injured or dysmyelinated spinal cord these investigations will have high impact.