Cell-derived therapy may help repair abnormal heart rhythm
Investigators found it also reduced scarred heart tissue in animals

Date:
April 12, 2022
Source:
Cedars-Sinai Medical Center
Summary:
Vesicles secreted from human heart cells may repair damaged tissue
and prevent lethal heart rhythm disorders, according to a new study.



FULL STORY ========================================================================== Vesicles secreted from human heart cells may repair damaged tissue and
prevent lethal heart rhythm disorders, according to a new study from investigators in the Smidt Heart Institute at Cedars-Sinai.


==========================================================================
The research, published in the European Heart Journal, could lead to a
new way to treat a heart rhythm problem called ventricular arrhythmia
-- a top cause of sudden cardiac death. In an accompanying editorial,
experts describe the research as "poised to turn this entire field on
its head." Repairing a Damaged Heart Ventricular arrhythmias can occur
after a heart attack damages tissue, causing chaotic electrical patterns
in the heart's lower chambers. The heart ends up beating so rapidly that
it cannot support the circulation, leading to a lack of blood flow and,
if untreated, death.

Current treatment options for ventricular arrhythmias caused by heart
attacks are far from ideal. These include medications with major side
effects, implanted devices to provide an internal shock, and a procedure
called radiofrequency ablation in which parts of the heart are purposely destroyed to interrupt disruptive electrical signals. Recurrence rates
are, unfortunately, high for all of these.

"Ablation is a counterintuitive approach because you are destroying
heart muscle in an already weakened heart," said Eugenio Cingolani, MD, director of the Cardiogenetics-Familial Arrhythmia Program at the Smidt
Heart Institute at Cedars-Sinai, and senior author of the study. "We
asked ourselves, 'What if instead of destroying damaged tissue, we tried
to repair it?'" With that in mind, the team sought to try a different
approach in laboratory pigs that experienced a heart attack. They
injected some of the laboratory pigs with tiny, balloon-like vesicles,
called exosomes, produced by cardiosphere- derived cells (CDCs), which
are progenitor cells derived from human heart tissue. Exosomes are hardy particles containing molecules and the molecular instructions to make
various proteins, thus they are easier to handle and transfer than the
parent cells, or CDCs.



==========================================================================
CDCs were first developed and characterized by Eduardo Marba'n, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the
Mark S.

Siegel Family Foundation Distinguished Professor. They have been used
in multiple clinical trials for a variety of diseases, most recently
Duchenne muscular dystrophy.

One group of pigs received an injection of CDC-derived exosomes in their
hearts and the other a placebo.

"The exosomes reduced the amount of scar tissue formed in the injured
regions of the heart, normalizing the rhythm without weakening the heart,"
said Dr.

Marba'n, who is a co-author on the study.

The animals were evaluated by MRI and tests to assess electrical stability
of the heart. Four to six weeks after injection, the laboratory pigs
that had received the exosome therapy showed markedly improved heart
rhythms and less scarring in their hearts.

A Novel Therapy In an editorial published in the same issue of
the European Heart Journal,Marine Cacheux, PhD, and Fadi G. Akar,
PhD, both of Yale University, summarize the pros and cons of various experimental gene- and cell-based approaches being studied for cardiac arrhythmias. Cedars-Sinai investigators "appear to have successfully
combined the best features of cell and gene therapies to address a major
unmet clinical need," according to Cacheux and Akar. The authors note
the approach used by Cedars-Sinai is novel in how it seeks to repair
scarring in the heart, and describe the study as "a paradigm- shifting
body of work."


==========================================================================
The investigators plan additional studies.

"More studies are needed to to know if the benefits observed in this
study persist over a longer period of time," said James F. Dawkins, DVM,
a research scientist at Cedars-Sinai and first author of the study,
"however, these preliminary results suggest the possibility for
a nondestructive alternative to treating ventricular arrhythmias."
Funding: This study was funded by the National Institutes of Health
under award numbers 1K01HL133510-01A1, R01HL135866 and R01HL14750

========================================================================== Story Source: Materials provided by Cedars-Sinai_Medical_Center. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. James F. Dawkins, Ashkan Ehdaie, Russell Rogers, Daniel Soetkamp,
Jackelyn Valle, Kevin Holm, Lizbeth Sanchez, Ileana Tremmel, Asma
Nawaz, Michael Shehata, Xunzhang Wang, Adityo Prakosa, Joseph Yu,
Jennifer E.

Van Eyk, Natalia Trayanova, Eduardo Marba'n, Eugenio Cingolani.

Biological substrate modification suppresses ventricular arrhythmias
in a porcine model of chronic ischaemic cardiomyopathy. European
Heart Journal, 2022; DOI: 10.1093/eurheartj/ehac042 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220412140949.htm

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