Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells.

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2022-11

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Abstract

Chronic kidney disease (CKD) affects 15% of the U.S. adult population, but the establishment of targeted therapies has been limited by the lack of functional models that can accurately predict human biological responses and nephrotoxicity. Advancements in kidney precision medicine could help overcome these limitations. However, previously established in vitro models of the human kidney glomerulus-the primary site for blood filtration and a key target of many diseases and drug toxicities-typically employ heterogeneous cell populations with limited functional characteristics and unmatched genetic backgrounds. These characteristics significantly limit their application for patient-specific disease modeling and therapeutic discovery. This paper presents a protocol that integrates human induced pluripotent stem (iPS) cell-derived glomerular epithelium (podocytes) and vascular endothelium from a single patient to engineer an isogenic and vascularized microfluidic kidney glomerulus chip. The resulting glomerulus chip is comprised of stem cell-derived endothelial and epithelial cell layers that express lineage-specific markers, produce basement membrane proteins, and form a tissue-tissue interface resembling the kidney's glomerular filtration barrier. The engineered glomerulus chip selectively filters molecules and recapitulates drug-induced kidney injury. The ability to reconstitute the structure and function of the kidney glomerulus using isogenic cell types creates the opportunity to model kidney disease with patient specificity and advance the utility of organs-on-chips for kidney precision medicine and related applications.

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10.3791/63821

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Roye, Yasmin, and Samira Musah (2022). Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells. Journal of visualized experiments : JoVE, 2022(189). 10.3791/63821 Retrieved from https://hdl.handle.net/10161/31829.

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Musah

Samira Musah

Assistant Professor in the Department of Biomedical Engineering

The Musah Lab is interested in understanding how molecular signals and biophysical forces can function either synergistically or independently to guide organ development and physiology, and how these processes can be therapeutically harnessed to treat human disease. Given the escalating medical crisis in nephrology as growing number of patients suffer from kidney disease that can lead to organ failure, the Musah Lab focuses on engineering stem cell fate for applications in human kidney disease, extra-renal complications, and therapeutic development. Dr. Musah’s research interests include stem cell biology and regenerative medicine, molecular and cellular basis of human organ development and disease progression, organ engineering, patient-specific disease models, biomarker identification, therapeutic discovery, tissue and organ transplantation, microphysiological systems including Organ Chips (organs-on-chips) and organoids, matrix biology, mechanotransduction and disease biophysics.


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