Schwann cells in the subcutaneous adipose tissue have neurogenic potential and can be used for regenerative therapies

TLDR: SAT-NSC transplant rescued functional deficits in mouse models of gastrointestinal dysmotility, suggesting that SAT could be a valuable source of NSCs with therapeutic potential for treating gastrointestinal motility disorders.

Abstract: Stem cell therapies for nervous system disorders are hindered by a lack of accessible autologous sources of neural stem cells (NSCs). In this study, neural crest–derived Schwann cells are found to populate nerve fiber bundles (NFBs) residing in mouse and human subcutaneous adipose tissue (SAT). NFBs containing Schwann cells were harvested from mouse and human SAT and cultured in vitro. During in vitro culture, SAT-derived Schwann cells remodeled NFBs to form neurospheres and exhibited neurogenic differentiation potential. Transcriptional profiling determined that the acquisition of these NSC properties can be attributed to dedifferentiation processes in cultured Schwann cells. The emerging population of cells were termed SAT-NSCs because of their considerably distinct gene expression profile, cell markers, and differentiation potential compared to endogenous Schwann cells existing in vivo. SAT-NSCs successfully engrafted to the gastrointestinal tract of mice, migrated longitudinally and circumferentially within the muscularis, differentiated into neurons and glia, and exhibited neurochemical coding and calcium signaling properties consistent with an enteric neuronal phenotype. These cells rescued functional deficits associated with colonic aganglionosis and gastroparesis, indicating their therapeutic potential as a cell therapy for gastrointestinal dysmotility. SAT can be harvested easily and offers unprecedented accessibility for the derivation of autologous NSCs from adult tissues. Evidence from this study indicates that SAT-NSCs are not derived from mesenchymal stem cells and instead originate from Schwann cells within NFBs. Our data describe efficient isolation procedures for mouse and human SAT-NSCs and suggest that these cells have potential for therapeutic applications in gastrointestinal motility disorders. Description Identification of the neural stem cell niche in fat tissue offers an accessible cell source for regenerative therapies. A fatty source of neural precursors The use of stem cells to repair the injured nervous system has shown promising results in experimental models. However, stem cell therapy development is limited by the paucity of available neural stem cells (NSCs). Here, Stavley et al. identified a population of Schwann cells in nerve bundles obtained from human and rodent subcutaneous fat tissue (SAT). In vitro, these cells acquired NSC properties. These SAT-NSCs integrated in the gastrointestinal tract in mice, migrated, differentiated into neurons and glial cells, and showed enteric neuron properties. SAT-NSC transplant rescued functional deficits in mouse models of gastrointestinal dysmotility, suggesting that SAT could be a valuable source of NSCs with therapeutic potential for treating gastrointestinal motility disorders.