gasconlab

Linea Investigación: Direct neuronal reprogramming for regenerative medicine.

Direct reprogramming of somatic cells into different lineages allows the generation of cell types that cannot otherwise be easily harnessed, such as human neurons from the central nervous system. This raises the exciting possibility of reprogramming-based therapies that may replenish cell populations using other cells surrounding an injured area in vivo. However, the efficiency of conversion is highly dependent of the cellular context where reprogramming occurs. In a previous study we investigated the influence that myeloid immune cells, that often infiltrate injured areas in the brain, exert in the efficiency of astroglia-to-neuron conversion, by using a coculture model with astroglia and macrophages. Our results determined that the presence of macrophages increases neuronal conversion efficiency of astrocytes, regardless of the transcription factor used for the reprogramming procedure. In this work we will delve into the cellular and molecular mechanisms by which macrophages enhance neuronal reprogramming. For that, we will determine whether this effect is mediated by released soluble molecules or by cell-cell contacts. Moreover, pro-inflammatory phenotypes of myeloid cells differ in acute and chronic diseases, being the former more associated to neuroprotection and the second with neurodegeneration. Therefore, in this work we also aim to explore the extent to which macrophage polarization towards more or less inflammatory phenotypes, influence neuronal reprogramming of astrocytes. These aspects are critical in order to design efficient reprogramming-based therapies approaches in the future treatment of different diseases of the CNS and at different stages.