Body-in-a-chip approach reveals how immune cells respond to heart injury

In a study published in Circulation Research, researchers at the Radcliffe Department of Medicine have developed a lab-grown human model that can capture how immune cells respond to heart injury in a dish – a major breakthrough in studying cardiac disease and repair.

Immune cells play a key role in cardiac injury and repair, shaping patient outcomes following heart attacks and other cardiac conditions. However, there are currently no human experimental models that can emulate those interactions in a dish. Unlike other organs, the human heart doesn’t regenerate, so patient biopsies can’t be used to provide relevant tissue to study. While immune cells can be taken from donor blood and added to engineered cardiac models, this approach is artificial, variable and difficult to scale. This has been a major roadblock in developing therapies and investigating the mechanisms that underpin cardiac injury and repair.

In this new study, researchers created a multi-organoid system by linking together human bone marrow and heart organoids – miniature, lab-grown versions of human organs derived from induced pluripotent stem cells.

The organoids were connected using a 3D-printed device, which allowed cells and fluid to move between them. When the heart organoid was subjected to injury, immune cells from the bone marrow organoid were recruited into the damaged tissue – mimicking, for the first time in a dish, the complex immune response to heart injury.

Microscope image showing the recruitment of immune cells (macrophages in green, monocytes in purple) to an injured cardiac organoid. [Image credit: Dr Julie Rayes, University of Birmingham]

 “This means we’ve added a vital missing component to experimental models of cardiac injury,” explained senior author Dr Abdullah Khan, RDM Principal Investigator at the MRC Weatherall Institute of Molecular Medicine. “It’s still astonishing that from just a handful of stem cells we can grow two different human organs and make them communicate with each other.”

During a global shift towards human experimental models, this platform offers a scalable and adaptable way to study immune-cardiac interactions. It can also be extended to include other organoid types, providing a powerful new tool for investigating disease mechanisms and testing therapies.

Co-lead author Dr Jasmeet Reyat, now a Research Fellow at Imperial’s National Heart and Lung Institute, said: “This system allowed us to model the recruitment of immune cells to an injured heart for the first time. Animal and fish models have major limitations, and a problem in the field of human modelling has been the lack of an immune component – which is so essential to the process of injury and repair. It opens up opportunities to study not just heart disease, but the many conditions where immune cells and tissues interact in health and repair.”

Read the full paper here: Human Multi-Organoid Platform to Model Immune Dynamics in Cardiac Injury and Disease