UM File # 6203
Advantagesare revolutionizing the drug discovery and development process used by pharmaceutical companies to identify lead drug candidates that provide opportunities to build innovative cellular models. Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell. The iPSC technology facilitates the development of diverse range of cellular models that represent a wide spectrum of drug susceptibilities and resistances, thereby offering a “clinical trial in a dish”. The use of stem cells in therapeutics and drug discovery has currently been focused on few major cell types, which includes cardiac cells. Despite the prospects of iPSCs in drug discovery, there are still several unmet challenges that slows down progress. One such challenge is the reprogramming strategy and maturation of human stem cell derived cardiovascular cells.
Novel method to obtain mature human stem cell derived cardiovascular cells for drug discovery and therapeutic applications
The generation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offers a revolutionary platform to transform the way heart disease is treated and to provide novel mechanistic insight into physiological and pathophysiological processes. Existing methods lead to generation of hiPSC-CMs with slow conduction velocities (CVs) that can be attributed to the immature structural and functional phenotype of the hiPSC-CMs generated to date. Researchers at the University of Michigan have demonstrated that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) monolayers plated on PDMS+matrigel had a mature electrophysiological phenotype with more negative resting membrane potentials, faster action potential upstrokes and faster CVs. They also show that the maturation process of hiPSC-CMs likely involves the activation of specific integrin signaling pathways that are sensitive to the hardness of the ECM. In addition, the inventors have produced and validated highly enriched and mature ventricular-like iPSC-CMs, derived from skin biopsy samples of patients carrying two separate mutations associated with an inheritable syndrome termed catecholaminergic polymorphic ventricular tachycardia (CPVT). This invention represents a significant advance toward the use of these promising cells for patient-specific disease modeling, drug testing and for development of autologous cellular therapies.
- Drug discovery
- Cardiotoxicity testing
- High throughput toxicity testing
- Disease specific drug testing
- Personalized medicine
- Regenerative medicine
- Fundamental research to build cellular models
- Mature cellular structure/function
- Faster maturation rate
- High throughput screening platform
- Personalized drug testing platform
- Disease specific drug testing platform