Therapeutic effect of myogenic cells modified to express neurotrophic factors in a rat model of sciatic nerve injury

Sciatic nerve injury may cause neurological deficits, particularly muscle weakness. Previous studies have shown that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, partially protected the damaged motor neuron in the injured sciatic nerve. In the current study, we have examined whether the administration of various combinations of transfected muscle progenitor cells (MPCs) populations, each expressing a single NTF (BDNF, GDNF, IGF-1 or VEGF) or conditioned media of such culture are capable of rescuing motor neurons in culture or in vivo. We have found that the mixture of conditioned media collected from cultured myogenic cells (MPCs- MIX⁺) alleviated the toxic effect of exposure of the motor neuron cell line NSC34 to hypoxic environment. Furthermore, NTFs secreting cells transplantation, protected motor neurons in a unilateral rat sciatic nerve injury model: One day after the crush, rats underwent transplantation at the lesion site with rat myogenic cells expressing one of the four NTFs; a mixture of cells expressing all four NTFs (MPCs- MIX⁺), MPCs-GFP or PBS. We found that in rats injected with MPCs- MIX⁺ the motor function was markedly preserved, compared to groups injected with cells secreting a single NTF, GFP or PBS. Transplantation of the MPCs- MIX⁺ significantly inhibited the degeneration of the neuromuscular junctions and enhanced the survival of the myelinated motor axons. The injection of MPCs- MIX⁺ preserved the compound muscle action potential (CMAP) as was demonstrated by motor nerve conduction studies. Our findings suggest that MPCs induced to secrete several NTFs can synergistically alleviate symptoms of sciatic nerve injury and perhaps other motor neuron disorders.