Biosensor-based profiling to track cellular signalling in patient-derived models of dilated cardiomyopathy
Kyla Bourque1, Cara Hawey1, Alyson Jiang1
1Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
Insights
Dilated cardiomyopathies (DCM) are complex heart conditions. New biosensor and stem cell technologies help researchers understand signaling pathways and develop personalized treatments for DCM patients.
Area of Science:
- Cardiovascular Research
- Cellular Signaling
- Regenerative Medicine
Background:
- Dilated cardiomyopathies (DCM) are heterogeneous cardiovascular diseases affecting myocardial structure and function.
- Understanding the impact of DCM on critical signaling pathways is crucial for developing effective therapeutic strategies.
- Advances in biosensor technology and human induced pluripotent stem cells (hiPSCs) offer novel approaches to study these complex diseases.
Purpose of the Study:
- To review the application of biosensor-based approaches and hiPSC-derived models in understanding DCM.
- To emphasize the importance of incorporating paracrine signaling in disease modeling.
- To discuss how these integrated approaches can inform patient-specific treatment strategies.
Main Methods:
- Utilizing biosensor-based approaches to study cellular signaling events in vitro and in vivo.
- Generating patient-derived hiPSC models to recapitulate individual cardiomyopathy phenotypes.
- Incorporating paracrine signaling mediators in multicellular culture systems.
Main Results:
- Biosensors enable real-time monitoring of signaling pathway dynamics in DCM models.
- hiPSC-derived cardiomyocytes provide patient-specific platforms for disease investigation.
- Multicellular models better reflect the complex cellular milieu and paracrine interactions in the heart.
Conclusions:
- The combination of biosensors and hiPSC technology offers powerful tools for dissecting DCM pathogenesis.
- Patient-derived models and advanced signaling analysis are key to developing personalized therapies for dilated cardiomyopathies.
- Future research should focus on integrating these advanced methodologies to accelerate therapeutic discovery for DCM.
Abstract:
Dilated cardiomyopathies (DCM) represent a diverse group of cardiovascular diseases impacting the structure and function of the myocardium. To better treat these diseases, we need to understand the impact of such cardiomyopathies on critical signalling pathways that drive disease progression downstream of receptors we often target therapeutically. Our understanding of cellular signalling events has progressed substantially in the last few years, in large part due to the design, validation and use of biosensor-based approaches to studying such events in cells, tissues and in some cases, living animals. Another transformative development has been the use of human induced pluripotent stem cells (hiPSCs) to generate disease-relevant models from individual patients. We highlight the importance of going beyond monocellular cultures to incorporate the influence of paracrine signalling mediators. Finally, we discuss the recent coalition of these approaches in the context of DCM. We discuss recent work in generating patient-derived models of cardiomyopathies and the utility of using signalling biosensors to track disease progression and test potential therapeutic strategies that can be later used to inform treatment options in patients.
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