Encouraging pre-clinical results for stem cells that can repair diseased cells signposts potential cure for heart failure patients.
A stem cell therapy treatment developed by Duke-NUS Medical School researchers for heart failure has shown promising results in preclinical trials. These cells, when transplanted into an injured heart, are able to repair damaged tissue and improve heart function, according to a study published in the journal npj Regenerative Medicine.
Longevity.Technology: The most common cause of death worldwide is ischemic heart disease, which is caused by diminished blood flow to the heart. When blood flow to the heart is blocked, the heart muscle cells die – a condition termed myocardial infarction or heart attack, something that happens to 805,000 people a year in the US [1].
In the Duke-NUS study, a unique new protocol was used where pluripotent stem cells were cultivated in the laboratory in order to grow into heart muscle precursor cells – these cardiomyocyte progenitors can develop into various types of heart cells, through a process called cell differentiation in which dividing cells gain specialised functions. During preclinical trials, the precursor cells were injected into the area of the heart damaged by myocardial infarction, where they were able to grow into new heart muscle cells, restoring damaged tissue and improving heart function.
“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 Dr Lynn Yap, an assistant professor at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore and first author on the study [2].
Previous research in studies conducted by other groups had ended less encouragingly – the transplantation of heart muscle cells that were already beating, brought about fatal side effects, causing ventricular arrhythmia, a sequence of abnormal heartbeats that can limit or stop the heart from supplying blood to the body.
To avoid this rather catastrophic outcome, the Duke-NUS researchers instead transplanted non-beating heart cells into the damaged heart. After the transplantation, the cells expanded and acquired the rhythm of the rest of the heart – beating to the same drum, as it were.
With this new procedure, the incidence of arrhythmia was cut by half. Even when the condition was detected, most episodes were temporary and resolved themselves on their own in around 30 days. In addition, the transplanted cells did not trigger tumour formation – another common and worrying 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’ CVMD Programme and the senior author of the study [2].
Professor Tryggvason, who is also the Tanoto Foundation Professor in Diabetes Research, is now leading other studies to adapt this regenerative medicine method for patients with diabetes, macular degeneration in the eyes and those needing skin grafts.
Underpinning all these studies is a controllable, stable and reproducible method to make the right cells for transplantation using laminins – glycoproteins that have a major role in the interactions of cells with their surrounding structures, regulating myriad cellular activities and signaling pathways.
Laminins exist in different forms depending on their environment and play a key role in directing the development of specific tissue cell types. In this study, stem cells were differentiated into heart muscle cells by growing them on the type of laminin found in abundance 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.
The technology has been licensed to Swedish biotech startup Alder Therapeutics earlier this year to further promote the development of cell-based regenerative cardiology. Using laminin LN-221, the team can generate cardiomyocyte progenitors from human embryonic stem cells in 9 to 11 days, paving the way for a safe and effective therapy for the regeneration of human heart muscle.
[1] https://www.cdc.gov/heartdisease/facts.htm
[2] https://www.duke-nus.edu.sg/allnews/stem-cell-therapy-treatment-for-heart-disease
