Stem cell-based regenerative therapy to treat heart failure

Researchers at Duke-NUS Medical School have led the development of a new stem cell therapy treatment for heart failure, which has shown promising results in preclinical trials as detailed in the journal npj Regenerative Medicine.

The most common cause of death worldwide is ischaemic 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.

The new study saw pluripotent (immature) stem cells cultivated in the laboratory to grow into heart muscle precursor cells, which can develop into various types of heart cells. This is done through cell differentiation, a process by 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,” said first author Dr Lynn Yap, who led the research while she was an assistant professor with Duke-NUS’s Cardiovascular & Metabolic Disorders (CVMD) Programme.

“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.”

In studies conducted by other groups, the transplantation of heart muscle cells that were already beating brought about fatal ventricular arrhythmia — abnormal heartbeats that can limit or stop the heart from supplying blood to the body. In contrast, the new procedure involves transplanting non-beating heart cells into the damaged heart; after the transplantation, the cells expanded and acquired the rhythm of the rest of the heart.

With this procedure, the incidence of arrhythmia was cut by half. Even when the condition 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,” said senior author Professor Karl Tryggvason, from the CVMD Programme. Tryggvason is also leading other studies to adapt the method for patients with diabetes, macular degeneration 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 — proteins that have a major role in the interactions of cells with their surrounding structures. 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 latest study, stem cells were differentiated into heart muscle cells by growing them on the type of laminin abundantly found in the heart.

“To ensure patient safety, it is imperative that cell-based therapies show consistent efficacy and reproducible results,” said co-author Associate Professor Enrico Petretto. “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.”

The technology was licensed to Swedish biotech startup Alder Therapeutics earlier this year.

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