Cell and Collagen Compositions for Engineered Cardiac Tissues for Regeneration
Overview
During a heart attack it is estimated that 1 billion cardiomyocytes (i.e. heart muscle cells) are killed. Unlike other organs in the body, the heart has a limited capacity to regenerate. This means that the cardiomyocytes lost during a heart attack are replaced by non-contractile scar tissue, resulting in decreased contractility and overall function of the heart. Heart regenerative strategies are aimed at introducing functional cardiomyocytes into the injured heart to re-muscularize, re-engineer its function and thus improve patient quality of life. Yet, current strategies do not address the massive number of cardiomyocytes that need to be delivered to the heart in order to have a therapeutically relevant impact on its function. The disclosed technology outlines the processes and compositions that support the formation of cell-dense, functional cardiac tissues that contain the appropriate number of cardiomyocytes for therapeutic impact.
Market Opportunity
Cardiovascular disease is the leading cause of death, impacting ~18 million people worldwide each year. Clinically, patients are increasingly surviving acute heart attack episodes due to quicker diagnosis and improved emergency interventions, but progress into heart failure due to the loss of functional heart muscle. Conventional treatments are focused on managing the symptoms of heart failure, rather than replacing the lost muscle. With ~50,000 HF patients in the United States becoming refractory to medical treatment each year, there is a critical need to develop novel therapies to restore contractility and enhance cardiac output after a heart attack. While other approaches to engineering cardiac tissue for heart regeneration feature low cardiomyocyte loads, the disclosed technology outlines the methods and compositions for scaling up engineered cardiac tissues in terms of both size and number of cardiomyocytes which is necessary for their clinical translation.
Innovation and Meaningful Advantages
Current compositions of engineered tissues for heart regeneration applications largely ignore the nonlinear nature of scaling up this system. The disclosed methods were developed with an enhanced knowledge of how scaling up impacts cardiac tissue formation and function in terms of structure, contractility and electrophysiology. The technology sources cardiomyocytes through differentiation of human induced pluripotent stem cells (SC), which represents a virtual limitless source of cells. By employing sophisticated cell culture purification and expansion techniques, >4 billion SC-derived cardiomyocytes can be generated at high purities of >70%. In order to scale up, an adaptable tissue molding system is used which is able to accommodate the physical scaleup of tissue size from 3x9mm to the human-relevant 65x75mm tissue. By employing a uniquely defined collagen hydrogel, 1 billion cardiomyocytes can be fabricated in a single large-scale tissue while maintaining its cardiac function. Further, this scaled tissue was successfully implanted in a preclinical model. The research team was awarded the Innovation of the Year (2023) award for this technology at the Innovation@Brown Showcase, which features the top innovative ideas emerging from Brown.
Collaboration Opportunity
We are interested in exploring research collaborations and licensing opportunities
References
Principal Investigator
Kareen L. K. Coulombe, PhD
Associate Professor of Engineering
Brown University
Kareen_Coulombe@brown.edu
https://vivo.brown.edu/display/kcoulomb
Contact
Melissa Simon, PhD
Director of Business Development
Brown Technology Innovations
melissa_j_simon@brown.edu
Brown Tech ID 3281