Giles W. Plant, Lorry I lokey Stem Cell Building, , Stanford, USA

Induced pluripotent stem cell derived motor neurons for the repair of acute cervical SCI

Funded in: 2014, 2015, 2016

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Problem: Regeneration of axons is impaired after spinal cord injury.

Target: Transplantation of iPS-cell derived neurons in combination with activation of the intrinsic axon growth capacity (PTEN inhibition)

Goal: Improvement of functional and anatomical repair after SCI

Regeneration of corticospinal tract (CST) axons is a major obstacle in the repair of the adult spinal cord after an injury. CST axons following injury fail to regenerate and retract rostrally from the original lesion site. For functional recovery, it is not only important that axons regrow just beyond the lesion site but it is vital to produce functional anatomical connections.

The project aims to demonstrate that transplantation of cortical motor neurons derived from human iPS will contribute to functional and anatomical repair after SCI through implementing an active relay graft and improve synaptic plasticity and circuitry.

Therefore, it combines
a) transplantation of specific cortical motor neurons derived from human iPS cells
b) activation of the intrinsic growth capacity of specific (forelimb) neurons in the cortex (PTEN signaling pathway) and
c) specific forelimb rehabilitation

Altogether, the project will provide important information to the use of differentiated iPS transplants for SCI.