Differentiated Mesenchymal Stem Cells for Sciatic Nerve Injury

Abstract

Sciatic nerve injury is common and may cause neurological deficits. Previous studies showed that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, preserved and protected damaged motor neuron in the injured sciatic nerve. We have been successful in converting bone marrow-derived mesenchymal stem cells into astrocyte-like cells that produce and secrete NTFs (NTF(+) cells). These cells demonstrate typical astrocyte morphology, express characteristic astrocyte markers and secrete high levels of NTFs. We have already shown that these cells and their conditioned media can protect neurons in culture and in animal models of neurodegenerative diseases. In the current study we examined whether NTF(+) cells are capable of rescuing motor neurons in a rat sciatic nerve injury model, where the right hind limb sciatic nerve was crushed. Rats were transplanted with NTF(+) cells, MSCs or PBS into the lesion site. In rats injected with the NTF(+) cells motor function was markedly preserved. Moreover, NTF(+) cells significantly inhibited the degeneration of the neuromuscular junctions and preserved the myelinated motor axons. Our findings suggest that autologous therapeutic approach can alleviate signs of sciatic nerve injury and probably other neurological disorders.