Related Experiment Video
Updated: Sep 8, 2025
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Toward Human Models of Cardiorenal Syndrome in vitro
Beatrice Gabbin1, Viviana Meraviglia1, Christine L Mummery1,2
1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands.
Insights
Developing advanced in vitro models is crucial for understanding cardiorenal syndrome (CRS), a complex heart and kidney disease. Human stem cells and microfluidic chips offer promising platforms for studying CRS mechanisms and developing new treatments.
Area of Science:
- Cardiorenal physiology and pathology
- Organ-on-a-chip technology
- Stem cell biology
Background:
- Cardiorenal syndrome (CRS) involves combined heart and kidney dysfunction, leading to significant morbidity and mortality.
- The complex, multifactorial mechanisms underlying CRS are not fully understood, hindering effective treatment development.
- Current in vivo models in rodents have limitations in manipulation, control, and human extrapolation.
Purpose of the Study:
- To review existing in vivo and in vitro models for studying cardiorenal syndrome (CRS).
- To identify the challenges and requirements for developing advanced in vitro models of CRS.
- To explore new perspectives for investigating heart-kidney interactions in vitro for therapeutic applications.
Main Methods:
- Review of current in vivo (rodent) and in vitro models of cardiorenal syndrome.
- Discussion of limitations of existing models, including interspecies differences and lack of dynamic crosstalk.
- Exploration of advanced in vitro approaches, such as human induced pluripotent stem cells and microfluidic chips.
Main Results:
- Existing in vivo models capture some cardiorenal interactions but are difficult to control and may not translate to humans.
- Independent in vitro models of heart and kidney exist, but none currently replicate dynamic organ-organ crosstalk.
- Human induced pluripotent stem cells combined with microfluidic technology show potential for recapitulating CRS in vitro.
Conclusions:
- Advanced in vitro human models are needed to gain insights into cardiorenal syndrome mechanisms.
- Developing in vitro models that capture dynamic heart-kidney crosstalk is essential for therapeutic development.
- Organ-on-a-chip systems using human stem cells represent a promising future direction for studying CRS.
Abstract:
Heart and kidney diseases cause high morbidity and mortality. Heart and kidneys have vital functions in the human body and, interestingly, reciprocally influence each other's behavior: pathological changes in one organ can damage the other. Cardiorenal syndrome (CRS) is a group of disorders in which there is combined dysfunction of both heart and kidney, but its underlying biological mechanisms are not fully understood. This is because complex, multifactorial, and dynamic mechanisms are likely involved. Effective treatments are currently unavailable, but this may be resolved if more was known about how the disease develops and progresses. To date, CRS has actually only been modeled in mice and rats in vivo. Even though these models can capture cardiorenal interaction, they are difficult to manipulate and control. Moreover, interspecies differences may limit extrapolation to patients. The questions we address here are what would it take to model CRS in vitro and how far are we? There are already multiple independent in vitro (human) models of heart and kidney, but none have so far captured their dynamic organ-organ crosstalk. Advanced in vitro human models can provide an insight in disease mechanisms and offer a platform for therapy development. CRS represents an exemplary disease illustrating the need to develop more complex models to study organ-organ interaction in-a-dish. Human induced pluripotent stem cells in combination with microfluidic chips are one powerful tool with potential to recapitulate the characteristics of CRS in vitro. In this review, we provide an overview of the existing in vivo and in vitro models to study CRS, their limitations and new perspectives on how heart-kidney physiological and pathological interaction could be investigated in vitro for future applications.
