RESUMO
To date, strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized ECM (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique cell culture platforms for personalized medicine.
Assuntos
Diferenciação Celular , Hidrogéis , Rim , Neovascularização Fisiológica , Organoides , Organoides/citologia , Hidrogéis/química , Humanos , Animais , Suínos , Rim/citologia , Diferenciação Celular/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Células-Tronco Pluripotentes/citologia , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacologia , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , AngiogêneseRESUMO
Los primeros ensayos clínicos han demostrado que la terapia celular puede mejorar el proceso de recuperación cardiaca tras la fase aguda del infarto de miocardio y la función cardiaca en la cardiopatía isquémica crónica. Sin embargo, algunos estudios han mostrado resultados contradictorios y aún existen dudas acerca de los mecanismos de acción y sobre la estrategia de tratamiento ideal para conseguir una mayor reparación cardiaca. En este capítulo se revisa la evidencia disponible actualmente, se analizan los ensayos clínicos de fases I y II y sus limitaciones, se discuten los puntos clave para el diseño de futuros estudios y se anticipa el futuro de los nuevos campos de investigación en este fascinante campo de la investigación cardiovascular traslacional (AU)
Previous clinical trials of stem cell therapy have demonstrated that the technique can promote the recovery of heart muscle after the acute phase of myocardial infarction and can improve cardiac function in chronic ischemic heart disease. However, some studies have produced conflicting results, and there are still questions about underlying mechanisms of action and about the best treatment strategy for optimizing cardiac repair. This article contains a review of recent findings in translational cardiovascular research and of the results and limitations of phase-I and -II clinical trials, discusses key issues in the design of future trials, and summarizes new areas for investigation in this fascinating field (AU)