@entity1 and XXXX Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is Aganglionic.

@entity1 @entity19 @entity16 @entity1109 @entity1963 @entity694
PURPOSE: @entity694 ( @entity694 ) might potentially replace absent or injured large intestine, but the enteric nervous system (ENS), a key component, has not been investigated. In various enteric @entity1109 in which the @entity694 is derived from aganglionic donor colon, the resulting construct might also be aganglionic, limiting tissue engineering applications in conditions such as @entity1963 ( @entity1963 ). We hypothesized that @entity694 might contain a diverse population of enteric neuronal subtypes, and that aganglionic @entity694 can be populated by neurons and glia when supplemented with ENS progenitor cells in the form of neurospheres. MATERIALS AND METHODS: @entity1 and @entity19 organoid units (OU) and multicellular clusters containing epithelium and mesenchyme were isolated from both @entity19 and @entity1 donor tissues, including from normally innervated and aganglionic colon. The OU were seeded onto a biodegradable scaffold and implanted within a host @entity19 , resulting in the growth of @entity694 . Aganglionic @entity19 and @entity1 OU were supplemented with cultured neurospheres to populate the absent ENS not provided by the OU to rescue the @entity1963 phenotype. RESULTS: @entity694 demonstrated abundant smooth muscle and clusters of neurons and glia beneath the epithelium and deeper within the mesenchyme. Motor and afferent neuronal subtypes were identified in @entity694 . Aganglionic OU formed @entity694 with absent neural elements, but neurons and glia were abundant when aganglionic OU were supplemented with ENS progenitor cells. CONCLUSION: @entity19 and @entity1 @entity694 contain key components of the ENS that were not previously identified, including glia, neurons, and fundamental neuronal subtypes. @entity694 derived from aganglionic colon can be populated with neurons and glia when supplemented with neurospheres. Combining tissue engineering and cellular replacement therapies represents a new strategy for treating enteric @entity16 , particularly @entity1963 .
