It’s a promising premise—to use stem cells to repair and regenerate irreversibly damaged tissues and organs like the heart. But one that remained unfulfilled for decades. Now, a team of scientists from Duke-NUS has brought the promise one step closer to reality for people with heart failure.

Using a novel laminin-based protocol to coax stem cells into heart muscle precursor cells, Dr Lynn Yap, who was then an assistant professor with Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, demonstrated that once these non-beating heart stem cells are injected into the heart, they grow into fully pumping heart muscle cells, healing damaged tissue and restoring heart function.

“Our technology brings us a step closer to offering a new treatment for heart failure patients, who would otherwise live with diseased hearts and have slim chances of recovery.”

Professor Karl Tryggvason

“As early as four weeks after the injection, there was rapid engraftment, which means the body is accepting the transplanted stem cells. We also observed the growth of new heart tissue and an increase in functional development, suggesting that our protocol has the potential to be developed into an effective and safe means for cell therapy,” said Yap, now an assistant professor at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 

Unlike previous efforts, the new protocol calls for transplanting non-beating heart cells instead of fully developed beating heart muscle cells, or cardiomyocytes.
 
“These [already] have their own rhythm. So when you transplant something with its own rhythm into the heart, then there will be two conflicting pacemakers,” explained Yap.

By injecting clearly differentiated, non-beating heart muscle precursor cells, Yap and the team found that these cells more readily acquired the rhythm of the rest of the heart, cutting the incidence of irregular heartbeats, or arrhythmia, by half. Even when arrythmia, which can be fatal, was detected, most episodes were temporary and self-resolved in around 30 days. In addition, the transplanted cells did not trigger tumour formation—another common concern when it comes to stem cell therapies.  

“Our technology brings us a step closer to offering a new treatment for heart failure patients, who would otherwise live with diseased hearts and have slim chances of recovery. It will also have a major impact in the field of regenerative cardiology, by offering a tried-and-tested protocol that can restore damaged heart muscles while reducing the risk of adverse side effects,” said Professor Karl Tryggvason from Duke-NUS’ Cardiovascular and Metabolic Diseases Programme and the senior author of this preclinical research, which was published in the journal npj Regenerative Medicine.

Tryggvason, who is also the Tanoto Foundation Professor in Diabetes Research, has been investigating the potential of laminins, a family of human proteins that play a key role in directing the development of specific tissue cell types, for three decades. And this latest protocol relies on a laminin that is found abundantly in the heart. 

“To ensure patient safety, it is imperative that cell-based therapies show consistent efficacy and reproducible results. By extensive molecular and gene expression analyses, we demonstrated that our laminin-based protocol for generating functional cells to treat heart disease is highly reproducible,” said Associate Professor Enrico Petretto, co-author of the study and Director of the Centre for Computational Biology at Duke-NUS.  

For Yap, these developments are encouraging on a professional level and quietly satisfying on a personal one.  

“My favourite uncle suffered from heart disease. That made me think about how important the heart was. He went through bypass [surgery] many times—that managed to sustain him for about ten years—but his heart was failing, and he eventually passed away,” shared Yap.  

With the technology licensed to a Swedish biotech startup in March 2023, she hopes this stem cell therapy will be able to help more heart disease patients like her uncle in the near future.