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Kidney Fibrosis In Vitro and In Vivo Models: Path Toward Physiologically Relevant Humanized Models
Gabriele Addario1, Lorenzo Moroni1, Carlos Mota1
1Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, ER Maastricht, 6229, The Netherlands.
Abstract:
Chronic kidney disease (CKD) affects over 10% of the global population and is a leading cause of mortality. Kidney fibrosis, a key endpoint of CKD, disrupts nephron tubule anatomy and filtration function, and disease pathomechanisms are not fully understood. Kidney fibrosis is currently investigated with in vivo models, that gradually support the identification of possible mechanisms of fibrosis, but with limited translational research, as they do not fully recapitulate human kidney physiology, metabolism, and molecular pathways. In vitro 2D cell culture models are currently used, as a starting point in disease modeling and pharmacology, however, they lack the 3D kidney architecture complexity and functions. The failure of several therapies and drugs in clinical trials highlights the urgent need for advanced 3D in vitro models. This review discusses the urinary system's anatomy, associated diseases, and diagnostic methods, including biomarker analysis and tissue biopsy. It evaluates 2D and in vivo models, highlighting their limitations. The review explores the state-of-the-art 3D-humanized in vitro models, such as 3D cell aggregates, on-chip models, biofabrication techniques, and hybrid models, which aim to mimic kidney morphogenesis and functions. These advanced models hold promise for translating new therapies and drugs for kidney fibrosis into clinics.
Insights
Advanced 3D kidney models offer improved human physiology simulation for studying chronic kidney disease (CKD) and fibrosis. These models promise better drug development for kidney fibrosis, addressing limitations of current 2D and in vivo approaches.
Area of Science:
- Nephrology
- Biomedical Engineering
- Translational Medicine
Background:
- Chronic kidney disease (CKD) impacts over 10% of the global population, with kidney fibrosis being a critical factor in disease progression and mortality.
- Current research models, including in vivo and 2D in vitro systems, have limitations in fully replicating human kidney physiology, metabolism, and molecular pathways.
- The failure of numerous therapies in clinical trials underscores the need for more advanced models to study kidney fibrosis.
Purpose of the Study:
- To review the limitations of existing 2D and in vivo models for studying kidney fibrosis.
- To explore the potential of state-of-the-art 3D humanized in vitro models for advancing kidney disease research.
- To highlight how these advanced models can improve the translation of therapies for kidney fibrosis.
Main Methods:
- Review of current literature on kidney disease models, including 2D cell cultures and in vivo studies.
- Exploration of advanced 3D in vitro modeling techniques such as 3D cell aggregates, organ-on-a-chip, and biofabrication.
- Discussion of diagnostic methods for kidney diseases, including biomarker analysis and tissue biopsy.
Main Results:
- Existing 2D and in vivo models inadequately represent human kidney complexity and function, hindering translational research.
- 3D humanized in vitro models, including organoids and bioengineered constructs, show promise in mimicking kidney morphogenesis and function.
- These advanced models offer a more physiologically relevant platform for studying kidney fibrosis mechanisms.
Conclusions:
- Advanced 3D in vitro models represent a significant improvement over traditional methods for studying kidney fibrosis.
- These models have the potential to accelerate the development and clinical translation of novel therapeutics for chronic kidney disease.
- Further development and validation of 3D kidney models are crucial for advancing nephrology research and patient care.
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