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News > InnovationNew regenerative stem cell therapy for heart disease shows
promise


NEW REGENERATIVE STEM CELL THERAPY FOR HEART DISEASE SHOWS PROMISE

Author: Eleanor Garth  |  Published on: June 29, 2023  |  Last updated: June 29,
2023



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.

Image on the left shows surgically-induced heart failure whereas the image on
the right shows recovery after heart precursors transplantation. The areas in
purple represent healthy tissue while areas in other colours show injured
tissue. Photograph: Professor Karl Tryggvason & Dr Lynn Yap, DukeNUS Medical
School

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



PHOTOGRAPH: PROFESSOR KARL TRYGGVASON & DR LYNN YAP, DUKENUS MEDICAL SCHOOL

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