Ashwani Kumar Gupta

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Research

Ashwani Kumar Gupta, PhD, is a Research Assistant Professor of Surgery at the University of Arizona. Dr. Gupta’s research work has been focused to study kidney development and disease. Diseases of the kidneys are common and debilitating, often with limited treatment options. There is no curative treatment available for the patients with chronic kidney diseases except renal transplantation. The lack of availability of transplant organs warrants research into technologies to understand how new kidney tissues can be generated. In the recent years, generation of kidney organoids from stem cells has become an important technology, with potential translational applications. Dr. Gupta’s research interest is to understand the pathways that regulate kidney stem/progenitor cell self-renewal and differentiation, in order to generate transplantable kidney tissues. His current research is focused to generate 3D organs using de-cellularized organ scaffolds, physiologically functional kidney organoids with glomerular filtration apparatus and interconnecting nephrons with collecting ducts/ureter. Dr. Gupta’s primary goal is to generate transplantable kidney tissues for the patients with end stage renal diseases.

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Scholarly Contributions

Journals/Publications

Proceedings Publications

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  ABSTRACT Recent years have seen rapid advances in directed differentiation of human pluripotent stem cells (PSCs) to kidney cells. However, a fundamental difficulty in emulating kidney tissue formation is that kidney development is iterative. Recent studies argue that the human nephron forms through gradual contribution of nephron progenitor cells whose differentiation fates depend on the time at which they are recruited. We show that the majority of PSC-derived nephron progenitor cells differentiated in a short wave in organoid formation and to improve fidelity of PSC-derived organoids, we emulated the asynchronous mix found in the fetal kidney by combining cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and lineage marking data showed that proximal and distal nephron components preferentially derive from cell populations differentiated at distinct times. When engrafted under the kidney capsule these heterochronic organoids were vascularized and displayed essential features of kidney tissue. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed using intravenous injection of fluorescent dextran. Despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study, and we propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop the same stromal overgrowth when engrafted under the kidney capsule.