Present and future avenues of cell-based therapy for brain injury: The enteric nervous system as a potential cell source

Abstract

Cell therapy is a promising strategy in the field of regenerative medicine; however, several concerns limit the effective clinical use, namely a valid cell source. The gastrointestinal tract, which contains a highly organized network of nerves called the enteric nervous system (ENS), is a valuable reservoir of nerve cells. Together with neurons and neuronal precursor cells, it contains glial cells with a well described neurotrophic potential and a newly identified neurogenic one. Recently, enteric glia is looked at as a candidate for cell therapy in intestinal neuropathies. Here, we present the therapeutic potential of the ENS as cell source for brain repair, too. The example of stroke is introduced as a brain injury where cell therapy appears promising. This disease is the first cause of handicap in adults. The therapies developed in recent years allow a partial response to the consequences of the disease. The only prospect of recovery in the chronic phase is currently based on rehabilitation. The urgency to offer other treatments is therefore tangible. In the first part of the review, some elements of stroke pathophysiology are presented. An update on the available therapeutic strategies is provided, focusing on cell- and biomaterial-based approaches. Following, the ENS is presented with its anatomical and functional characteristics, focusing on glial cells. The properties of these cells are depicted, with particular attention to their neurotrophic and, recently identified, neurogenic properties. Finally, preliminary data on a possible therapeutic approach combining ENS-derived cells and a biomaterial are presented.

Keywords: brain injury; cell therapy; enteric nervous system; glia; hydrogels.