Delivery of Mesenchymal Stem Cells from Gelatin-

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICC) and 19 enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and 20 delayed gastric-emptying. Regenerating these fundamental structures with stem cell therapy, 21 would be helpful to restore gastric function in GP. Mesenchymal stem cells (MSC) have been 22 successfully used in animal models of other gastrointestinal (GI) diseases including colitis. 23 However, no study has been performed with these cells on GP animals. In this study, we explored 24 if mouse MSC can be delivered from a hydrogel-scaffold to the luminal surfaces of GP mice stomach. 25 Mouse MSC was seeded atop alginate-gelatin, coated with poly-L-lysine. These cell-gel constructs 26 were placed atop stomach explants facing the luminal side. MSC grew uniformly all across the gel 27 surface within 48 hr. When placed atop the lumen of the stomach, MSC migrated from the gels to 28 the tissues as confirmed by positive staining with Vimentin and N-cadherin. The feasibility of 29 transplanting a cell-gel construct to deliver stem cells in the stomach wall was successfully shown 30 in a mice GP model, thereby making a significant advance towards envisioning the transplantation 31 of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with stem cells, and growth factors. 32