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  • Title: Smooth muscle from aganglionic bowel in Hirschsprung's disease impairs neuronal development in vitro.
    Author: Langer JC, Betti PA, Blennerhassett MG.
    Journal: Cell Tissue Res; 1994 Apr; 276(1):181-6. PubMed ID: 8187159.
    Abstract:
    Hirschsprung's disease results from the congenital absence of enteric neurons in human distal colon. The reason for aganglionosis is unknown but may reflect an unfavourable microenvironment for neuronal development. We asked if smooth muscle cells from the anganglionic region could affect neuronal development in vitro. Neurons from neonatal mouse superior cervical ganglia were added to cultures of smooth muscle obtained from normal or aganglionic regions of five patients with Hirschsprung's disease. Although neurons initially showed more rapid attachment to aganglionic smooth muscle, this was equal by 60 min and thereafter. Progressive increase in the diameter of the nerve cell body was characteristic of normal maturation in vitro. This was consistently inhibited by 15-22% in neurons grown on aganglionic muscle compared with normal controls over the 6-day test period (P < 0.05). This phenomenon was preserved when the smooth muscle cells were lysed by brief exposure to distilled water before initiation of co-culture (16-18% inhibition; P < 0.05). These data imply that smooth muscle of the aganglionic colon is less favourable for neuronal development than the normally innervated region and suggest a membrane-linked factor. Clearly, this persists in postnatal life and in vitro and may reflect an abnormality of cellular interaction causing Hirschsprung's disease.
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