Nephrogenesis on a chip: an simple modular platform to spatially pattern extracellular matrix, stromal cells, and soluble factors

Abstract It is well appreciated that the spatial organization of the biophysical and biochemical cues in the extracellular matrix (ECM) in concert with the stromal cell organization along the cortical-medullary axis of the developing kidney is vitally important to nephron development. These insights have been obtained from animal and organoid models, however, the exact mechanisms behind the tightly regulated spatial and temporal differentiation and cell specification have not been fully established. Although reductionistic, an in vitro microphysiological system (MPS) offers a platform that allows recapitulation and control of the developing kidney's critical structural and functional components. Here, we develop an easy-to-use modular 3D model of the developing nephron in which the biophysical and biochemical cues of the ECM, soluble factors, and stromal cell identity can be spatially patterned along the length of an epithelialized tube (Aim 1). In Aim 2, we will create a framework for MPS fabrication and model establishment to enable wide distribution and technology transfer to other labs that are established experts in investigating different aspects of nephrogenesis and renal pathology but non-experts in using microfluidic in vitro models. This easy-to-use system will provide researchers without MPS expertise with a tool to investigate the role and mechanisms of biochemical, cell-cell, and cell-ECM interactions during nephrogenesis. As such, this model will be designed to be quickly and easily disseminated to the research community to rapidly increase mechanistic investigation of nephrogenesis for biological understanding, pharmacological screening, and tissue engineering applications.