Cotransplantation of neuroepithelial stem cells with interstitial cells of Cajal improves neuronal differentiation in a rat aganglionic model

Background: Recent advances have raised the possibility of treating Hirschsprung's disease (HSCR) with transplanted neural stem cells. Although these cells have been shown to migrate and differentiate after transplantation, the restoration of intestinal motility by grafted cells is also mediated via the interstitial cells of Cajal (ICCs). We therefore aimed to evaluate the effect of cografting with ICC on neural stem cells after transplanted into aganglionic bowel. Methods: Neuroepithelial stem cells (NESCs) and ICCs were isolated from neural tube of embryonic rat (embryonic day 11.5) and colon of neonatal rats respectively. After cotransplantation into the benzalkonium chlorideinduced rat aganglionic colon, survival and differentiation of the implanted cells were assessed 8 weeks posttransplantation using immunofluorescence and Western blotting. Colonic motility was assessed by measuring the changes of intraluminal pressure responding to inflating stimulation and the response of muscle strips to electrical field stimulation. Results: Cotransplantationwith ICC accelerated neuronal differentiation comparedwith transplantation of NESCs alone. Moreover, the contractile response to inflation and EFS-induced reaction of the colon after coimplantation were successfully evoked. Conclusions: These data indicate that reconstitution of elements in the intestinal environment such as ICC enhances efficacy of NESCs therapy. This may aid development of a stem cell-based treatment for HSCR. (C) 2017 Elsevier Inc. All rights reserved.