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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Imaging Studies I: Kidney, Ureter, and Bladder Studies01:28

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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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Human Pluripotent Stem Cell-Derived Kidney Model for Nephrotoxicity Studies.

Piyush Bajaj1, A David Rodrigues2, Claire M Steppan2

  • 1Discovery Sciences (P.B., C.M.S., S.J.E., T.S.) and Pharmacokinetics, Dynamics, and Metabolism (A.D.R., S.M.), Pfizer Worldwide Research and Development, Pfizer Inc., Groton, Connecticut Thomas.Schroeter@pfizer.com Piyush.Bajaj@takeda.com.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
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This study developed a human pluripotent stem cell (hPSC)-derived kidney model to predict drug-induced kidney injury. The model successfully distinguished nephrotoxic compounds by measuring specific kidney injury markers.

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Area of Science:

  • Stem cell biology
  • Nephrology
  • Toxicology

Background:

  • Current in vitro models for identifying nephrotoxins have limited predictive power.
  • Developing accurate predictive models is crucial for drug safety and development.

Purpose of the Study:

  • To evaluate a human pluripotent stem cell (hPSC)-derived three-dimensional kidney model as a platform for predicting nephrotoxicity.
  • To assess the model's ability to differentiate between nephrotoxic and benign compounds and identify mechanisms of toxicity.

Main Methods:

  • Differentiated hPSCs into three-dimensional multicellular structures containing proximal tubule cells (PTCs) and podocytes.
  • Assessed cellular functions including endocytosis and transporter activity (e.g., ABC, SLC, OAT1, OAT3, OCT2, OCTN2, OATP4C1, MATEs).
  • Treated the model with 10 pharmacologic agents and measured tubular (KIM-1, HO-1) and glomerular (NPHS1, WT1) markers of kidney injury.

Main Results:

  • PTCs demonstrated megalin-dependent endocytosis and active gamma-glutamyl transpeptidase.
  • Functional activity of key renal transporters (OCTN2, OATP4C1, OCTs/MATEs) was confirmed.
  • The model distinguished known nephrotoxic agents from benign compounds by detecting increased kidney injury markers, allowing for differentiation of toxin types.

Conclusions:

  • The hPSC-derived kidney model shows promise for detecting mechanistically diverse nephrotoxins.
  • Further improvement in key renal transporter expression could enhance the model's predictive capabilities.
  • This model offers a potential advancement over current in vitro nephrotoxicity testing methods.