Recent developments in cell-based ENS regeneration - a short review

Abstract

Therapeutic options to treat neurogenic motility disorders of the gastrointestinal tract are usually limited to symptomatic treatment. The capacity of the enteric nervous system (ENS) to regenerate and the fact that progenitor cells of the enteric nervous system reside in the postnatal and adult gut led to the idea to develop cell-based strategies to treat ENS related disorders. This short review focuses on recent developments in cell-based ENS regeneration, discussing advantages and disadvantages of various cell sources, functional impact of transplanted cells and highlights the challenges of translation of small animal studies to human application.

Keywords: Hirschsprung disease; cell therapy; enteric nervous system; regeneration; stem cells.

©2018 Obermayr F., Seitz G., published by De Gruyter, Berlin/Boston.

Figures

Figure 1:

Schematic view of the important steps of ENS progenitor generation and transplantation. (A) Generation of ENS progenitor cells from patient-derived induced pluripotent stem (iPS) cells. Somatic cell can be reprogrammed to generate iPS cells, which can be differentiated into ENS progenitor cells [16]. Since the cells are patient-derived, disease-associated gene mutation might limit their proliferative, migratory and differentiation behavior. Thus, repair of the mutations might be necessary to rescue these defects, as described [16]. (B) Generation of ENS progenitor cells from pluripotent embryonic stem cells (ES cells) has been described by Fattahi et al. [17]. They were even able to demonstrate rescue of a HSCR mouse model by transplantation of generated ENS progenitors into the cecum of neonatal mice. (C) Generation of ENS progenitor cells derived from the patient’s gut. Isolation of the proper cell types relies on progenitor cell-specific cell surface markers. In contrast to ES or iPS cells, the self-renewal capacity of these cells is limited. Thus, optimizing the in vitro expansion condition is an important step in generating a sufficient number of cells that allows colonization of a large area.

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