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Generation of cartilage-free kidney organoids: a small molecule strategy

Objective

The prevalence of chronic kidney disease in Europe varies from 3.3–17.3% and has risen during the last decades. In the world, 9.7 million people need kidney replacement therapy, but only 2.6 million will receive it. These numbers are expected to double within the next 10 years, increasing the pressure to find alternative solutions. Recent scientific developments to generate kidney organoids in vitro have opened the possibility for a regenerative medicine–based approach that would provide a functional substitute to the failing kidney. These kidney organoids can recapitulate renal structures as well as the cellular complexity of human kidney, and may restore glomerular filtration upon transplantation.

In this project, we make use of human induced pluripotent stem cells that can be differentiated with a cocktail of biomolecules and aggregated to form of kidney organoids that are cultured at the air–liquid interface. This protocol leads to the formation of complex renal structures including glomeruli and tubules. While kidney organoids show great therapeutic potential, they also present several drawbacks, one of which is the appearance of off-target cell populations, such as neurons, myocytes and chondrocytes within the organoid. Preventing the appearance of these off-target cells will greatly improve the quality of the organoids. Preventing cartilage formation is most desirable because cartilage completely disrupts the organoids and renders them dysfunctional and unsuitable for in vivo use.

The reasons for the consistent observation of chondrocytes during organoid growth and transplantation are not yet understood. The objective of this work is to understand the molecular mechanisms of cartilage formation in kidney organoids and reduce it using a small molecule strategy.

Coordinator

UNIVERSITEIT MAASTRICHT
Net EU contribution
€ 203 464,32
Address
Minderbroedersberg 4
6200 MD Maastricht
Netherlands

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Region
Limburg (NL) Zuid-Limburg
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
No data