Therefore, using principles of tissue engineering, including isolated cells combined with appropriate biomaterials, can lead to the formation of a tissue-engineered stomach in vivo . the luminal surfaces of mice stomach explants. Mouse MSCs were seeded atop alginateCgelatin, coated with poly-l-lysine. These cellCgel constructs were placed atop stomach explants facing the luminal side. MSCs grew uniformly all across the gel surface within 48 h. When placed atop the lumen of the stomach, MSCs migrated from the gels to the tissues, as confirmed by positive staining with vimentin and N-cadherin. Thus, the feasibility of transplanting a cellCgel construct to deliver stem cells in the stomach wall was successfully shown in a mice stomach explant model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered gastric patch or microgels with cells and growth factors. Keywords: tissue engineering, lumen, stem cells, interstitial cells of Cajal, hydrogel scaffolds 1. Introduction Gastroparesis (GP) is a common gastrointestinal (GI) motility disorder characterized by delayed gastric emptying without any mechanical obstruction, and is known to affect almost 10 million individuals in the United States. Depletion or structural changes of interstitial cells of Cajal (ICCs) in the diseased gastric tissue  Prochloraz manganese have been noted in studies with Prochloraz manganese animal models, as well as in patients with GP. It is well known that ICCs function as the pacemakers of the GI tract, and are involved in the transmission of the neuronal signaling to the smooth muscles. Prochloraz manganese Therefore, their existence in the stomach wall is of prime importance for their properties of slow-wave generation and propagation, which allow for the movement of food through the digestive canal . Loss of ICCs is believed to result in conditions of gastroparesis, and may even lead to gastric cancer [2,3]. GP is also associated with the depletion of enteric neurons, including nitric oxide synthase (nNOS)-expressing neurons . The depletion of nNOS results in pyloric dysfunction and delayed gastric emptying . Treatment options are limited, with the most common treatment being surgical resection of the stomach or gastrectomy, however, post-gastrectomy, many patients suffer various unwanted after-effects including bloating, loss of appetite and malnutrition . Regenerative stem cell therapies, based on principles of tissue engineering, have been proposed as a therapeutic possibility to restore the levels of depleted ICCs and the normal physiological functions of the stomach wall . Previous studies adopted an acellular materials-based approach using collagen-based scaffolds to induce new tissue growth within the host [5,6,7], Prochloraz manganese but these efforts failed to restore function to the diseased stomach wall. Other cell-based approaches were centered on building stomachCepitheliumCorganoid units for overcoming the difficulties of isolating and culturing gastric epithelial cells in vitro . These efforts led to the development of vascularized tissue with a neo-mucosa, and also indicated the presence of a smooth muscle layer and gastric epithelium, as well as the existence of parietal cells of the stomach mucosa, post-implantation . However, the isolation of stomachCepitheliumCorganoid units is extremely challenging . We conceived an alternative, simpler and more feasible technique of delivering cells from hydrogel scaffolds to the stomach tissue lumen in vitro such that, if successful, this approach can then be translated in vivo. In this study, mouse mesenchymal stem cells (MSCs) were seeded atop BII an alginateCgelatin scaffold for placing on luminal surfaces of mouse stomach explants in vitro. The possibility of using bone marrow and other non-gut-derived murine MSC for in vivo immunosuppression after allogeneic transplantation is well established . We hypothesized that the mouse MSCs would adhere and proliferate within the alginateCgelatin scaffold, and upon being placed atop the stomach tissue, would Prochloraz manganese migrate from the gels to the actual tissue sections. The results yielded from this work will lead us to our long-term goal, to deliver MSCs or induced pluripotent stem cells (iPSCs) from a bioengineered scaffold to the host stomach wall, to help restore the depleted levels of ICCs and lead to regeneration of smooth muscle tissue leading to overall physiological improvement.
Therefore, using principles of tissue engineering, including isolated cells combined with appropriate biomaterials, can lead to the formation of a tissue-engineered stomach in vivo