Direct reprogramming of adult human olfactory ensheathing glia (OEG) into neurons

M Portela-Lomba(1,2) D Simón(1) M T Moreno-Flores(2) J Sierra(1)

1:Universidad Francisco de Vitoria; 2:Universidad Autónoma de Madrid

Different cell therapy strategies have been tried to heal Central Nervous System (CNS) injuries. A recent approach is the transplantation or in vivo generation of induced neurons (iNs) whose origin is direct reprogramming from mature glial cells. Direct cellular reprogramming consists in producing a differentiated cellular type from a somatic cell, without going through a pluripotent/stem cell stage. This has been achieved by transduction of viral vectors that express neurogenic transcription factors, with additional chemical manipulation.

We propose a unique cellular type as a candidate for direct reprogramming to iNs: olfactory ensheathing glia (OEG). OEG surrounds growing axons of sensory olfactory neurons and promotes axonal regeneration both in its physiological location (bulb and olfactory mucosa) as in in vitro and murine models of CNS injury. We suggest that engraftment of OEG and OEG induced neurons (OEG-iNs) would enhance neuroregeneration at the injured site. This would be due to the intrinsic axonal regenerative capacities of OEG, added to the presence of OEG-iNs which would mature to synapse forming neurons. OEG can be easily obtained from the patient´s olfactory mucosa and used for autologous transplantation.

We present the results of reprogramming adult human OEG into neurons (OEG-iNs), through the expression of the transcription factor NeuroD1. OEG-iNs have neuronal morphology, express general and mature neuronal markers and differentiate to glutamatergic neuronal subtype. Functionality has been achieved as OEG-iNs are capable of firing action potentials.