This project was born out of a critical need to make cell-based therapies for heart disease less invasive and more effective. Traditional methods involve directly injecting iPSC-CL cells into the heart muscle. This can be quite invasive for the patient and often results in limited engraftment due to volume constraints and the body’s natural immune response. Our cardiac spheroids offer the potential for a revolutionary alternative. Instead of direct injection, these spheroids would be delivered via catheter into a coronary artery. Their unique size and shape allow them to naturally lodge in the small vessels branching off the artery, ensuring targeted delivery without direct heart muscle injections. We hypothesize that this method will lead to significantly better iPSC-CL cell survival and a larger engraftment area, as cells that maintain their connections with each other tend to thrive.
Our immediate focus is to pinpoint the optimal cardiac spheroid size and dosage using our ex-vivo heart model. We can “customize” the spheroid size by adjusting the number of cells in each aggregate. Delivering multiple smaller doses over time via catheter could also enhance safety and engraftment. Understanding these parameters will allow us to determine the total number of iPSC-CL cells needed from a patient to create a clinical dose.
One of our biggest challenges has been developing a method to generate thousands of precisely sized cardiac spheroids efficiently, with minimal user intervention. Scaling this process is crucial for producing the quantities needed for clinical use. Our exciting solution? 3D printing custom molds to create our own cell culture plates. These plates feature thousands of microwells, guiding single cells to form spheroids of a predictable size. Looking ahead, we aim to automate the daily cell culture maintenance to further reduce handling requirements.
What truly excites and motivates us about this project is its clear path to clinical application. Every experiment brings us closer to proving our hypothesis: that this method will lead to superior iPSC-CL graft survival and engraftment compared to past single-cell injection techniques. Our driving force is always to improve patient outcomes, and seeing our work transition from the lab to the clinic will be the ultimate reward.
Our overarching goal at HeartWorks is the remuscularization of the heart, achieving a critical mass of new tissue sufficient for functional repair. It’s not enough to simply deliver cardiac spheroids; they must functionally integrate with the host tissue over time. Our next major milestone will be to assess the long-term survival of cardiac spheroids in the heart, allowing us to determine if this method leads to efficient remuscularization. This project holds immense promise for revolutionizing cardiac care and offering new hope to patients with heart disease.
To learn more about this project, please email hello@webuildhearts.org
