Producing heart cells from iPSCs faster and more cost-effectively

MHH researchers receive millions in funding from the European Union to improve a production platform for personalized cell therapy.

Heart failure is one of the leading causes of death worldwide. Treatment options are limited, especially when heart failure is caused by congenital heart defects. Affected individuals require mechanical circulatory support or an organ transplant as early as young adulthood. Both options have drawbacks: cardiac support systems require permanent blood thinning and are not a permanent solution; donor hearts are rare and require lifelong immunosuppression. An alternative is the use of so-called human induced pluripotent stem cells (hiPSCs). These genetically reprogrammed somatic cells can develop into any cell type-for example, into heart muscle cells. Such laboratory-grown cardiomyocytes (hiCMs) are intended to replace lost heart muscle tissue and improve heart function in the future. If the hiPSCs are derived not from donated somatic cells but from the recipients themselves, immunosuppression is not even necessary. This is because the immune system does not recognize the cells derived from the body's own, autologous hiPSCs as foreign. However, their production has so far been very labor-intensive and expensive.

A research team led by Prof. Dr. Robert Zweigerdt, a cell biologist at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at the Clinical Department of Cardiac, Thoracic, Transplant, and Vascular Surgery at Hannover Medical School (MHH), and LEBAO Director Prof. Dr. Ulrich Martin aims to solve this problem. With their iNDUCARE project, they aim to utilize a manufacturing process for autologous hiCMs that is already approved in the U.S. and improve it so that personalized heart repair becomes affordable and clinically feasible in the future. The European Union is funding this international collaborative project with a total of eight million euros. As the coordinator, MHH will receive approximately two million euros of this amount.

Immunosuppression is problematic

"A major advantage of transplanting hiCMs produced from the body's own, so-called autologous blood cells is that no immunosuppression-which is associated with side effects-is required, which is a decisive advantage, particularly for children and young adults," notes Professor Martin. From a commercial perspective, the mass production of cell products derived from exogenous (allogeneic) iPS cells may seem attractive due to lower upfront costs compared to patient-derived iPSCs. However, significantly higher costs would arise in the long term because lifelong immunosuppression is generally required. Prof. Dr. Arjang Ruhparwar, Director of HTTG Surgery, adds: "Drug-induced immunosuppression is also problematic for patients in critical condition because their immune systems cannot tolerate further impairment. But such treatment is also unjustifiable for children and young adults given the high risks of infection, tumor development, and reduced quality of life."

Production still too time-consuming and expensive

In the long term, the autologous approach could therefore even be more cost-effective and sustainable in many cases than therapy with allogeneic iPSCs derived from another individual. However, in addition to the significantly higher costs at the start of treatment, there are two further reasons why this therapy has not yet become widely established. On the one hand, each cell line must not only be individually established but also produced through complex manufacturing processes and quality-tested to guarantee the desired function and rule out treatment risks. On the other hand, for acute heart diseases, it takes too long to produce a sufficient quantity of these cells for treatment.

AI-supported quality control

The complex production processes are to be further improved in iNDUCARE. Newly developed sendavirus vectors are intended to shorten the reprogramming process and reduce costs. The researchers aim to address the second problem with the help of high-density stirred-tank bioreactors. "So far, the required cell counts can only be produced in large two-liter bioreactors," says Professor Zweigerdt. "AI will be used to optimize production processes and quality controls: We aim to produce a sufficient treatment dose in just 300 milliliters-roughly the volume of a large coffee mug."

Using the platform for other applications as well

The researchers aim to compare MHH's current production processes with the manufacturing process already in use in the U.S. Combining elements of both technologies is expected to result in an improved hiCMs production platform that can be used in both Europe and the U.S. for the production of autologous iPS products. "We expect a five- to sevenfold increase in cardiomyocyte yield while simultaneously reducing production time from one year to seven months and cutting costs by up to 70 percent," explains Professor Zweigerdt. "And all of this without compromising on safety or quality." The researchers aren't just focusing on the heart muscle. "Our manufacturing platform is also intended to be transferable to other cell-based therapies and to lay the foundation for next-generation patient-specific treatments that go beyond heart repair," emphasizes Professor Martin.

The iNDUCARE collaborative project will launch on September 1, 2026, and will run for four years. In addition to MHH, the project involves partners from research, industry, and Clinical Departments in Germany, the United Kingdom, Israel, the Netherlands, Switzerland, the Czech Republic, and the United States.

Text: Kirsten Pötzke