Restoring mucosal barrier function and modifying macrophage phenotype with an extracellular matrix hydrogel: potential therapy for ulcerative colitis

Background & Aims: Despite advances in therapeutic options, more than half of all patients with ulcerative colitis (UC) do not achieve long-term remission, many require colectomy, and the disease still has a marked negative impact on quality of life. Extracellular matrix (ECM) bioscaffolds facilitate the functional repair of many soft tissues by mechanisms that include mitigation of pro-inflammatory macrophage phenotype and mobilization of endogenous stem/progenitor cells. The aim of the present study was to determine if an ECM hydrogel therapy could influence outcomes in an inducible rodent model of UC. Methods: The dextran sodium sulfate (DSS)-colitis model was used in male Sprague Dawley rats. Animals were treated via enema with an ECM hydrogel and the severity of colitis was determined by clinical and histologic criteria. Lamina propria cells were isolated and the production of inflammatory mediators was quantified. Mucosal permeability was assessed in-vivo by administering TRITC-dextran and in-vitro using transepithelial electrical resistance (TEER). Results: ECM hydrogel therapy accelerated healing and improved outcome. The hydrogel was adhesive to colonic tissue, which allowed for targeted delivery of the therapy, and resulted in a reduction in clinical and histologic signs of disease. ECM hydrogel facilitated functional improvement of colonic epithelial barrier function and the resolution of the pro-inflammatory state of tissue macrophages. Conclusions: The present study shows that a nonsurgical and nonpharmacologic ECM-based therapy can abate DSS-colitis not by immunosuppression but by promoting phenotypic change in local macrophage phenotype and rapid replacement of the colonic mucosal barrie

Differentiation of iPSCs into Cardiomyocytes Utilizing Extracellular Matrix

According to the American Heart Association, Ischemic heart disease is the principal cause of death. Many potential therapies are being simultaneously explored and among the most promising is tissue engineering of cardiac scaffolds. In vitro culturing of mature cardiomyocytes has the potential to lay the foundation for products such as cardiac patches for treatment of early stages of Ischemic heart disease or atrial septal defects, and developing entire replacement hearts. However, cardiomyocyte cell culture and experimentation has encountered various difficulties; the inability to proliferate, incomplete maturation, and having a small window of functional contraction. Conversely, iPSCs can partially differentiate into cardiac progenitor cells, adhere to a surface, then continue to proliferate prior to maturation into cardiomyocytes. Vitronectin is the most prevalent cell adhesive protein used for stem cell culture, however it is not usable as an implant scaffold or for clinical applications. Extracellular matrix (ECM) is a natural protein structure that provides a scaffold, growth factors, and other necessary components for tissues and organs. Due to the abundance of signaling proteins contained in ECM, it is a prime candidate to be used as a structural foundation for various cell lines. The objective of this project was to differentiate iPSCs into cardiomyocytes on Vitronectin or cardiac ECM (cECM) and then characterize the results to determine their relative feasibility as tools in future translational research