AsianScientist (Aug. 29, 2019) – A research group in Hong Kong has developed a multipronged approach involving two types of stem cells for concurrently rejuvenating both the muscle cells and vascular system of the heart. They published their findings in the journal Nature Communications.
Myocardial infarction (MI), more commonly known as a heart attack, leads to permanent loss of heart muscle cells, or cardiomyocytes (CMs), and scar tissue formation. The damage to cardiac function is often irreversible.
With limited therapeutic options for severe MI and advanced heart failure, a heart transplant is the last resort. However, the procedure is very risky, costly and subject to limited suitable donors. Therefore, stem cell-based therapy has emerged as a promising therapeutic option.
In this study, scientist led by Dr. Ban Kiwon at the City University of Hong Kong sought to use stem cells to promote cardiac regeneration.
“The heart is an organ composed of cardiac muscles and blood vessels, where vessels are essential to supply oxygen and energy to the muscles. Since both cardiac muscles and [the associated] vasculature would be severely damaged following MI, therapeutic strategies should focus on comprehensive repair of both [the muscles and blood vessels] at the same time. But so far, treatment strategies only focus on either one,” he explained.
Hence, his team decided to use human bone marrow derived mesenchymal stem cells (hMSCs) and cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) simultaneously. The role of hMSCs was to secrete factors that promote the regeneration of blood vessels and endothelial cell survival. Concurrently, hiPSC-CMs were used because of their similarities with human primary CMs in terms of the expression of cardiac-specific genes, structural proteins, ion channels and, more importantly, ability to contract spontaneously.
The researchers demonstrated that their dual approach led to a significant improvement of cardiac function and enhancement of vessel formation in mice hearts. The implanted hMSC-loaded patch not only provided a microenvironment which enhanced vascular regeneration as expected, but also improved the retention of hiPSC-CMs, ultimately augmenting heart function and restoring the injured myocardium.
Moreover, histological analyses revealed that implantation of the hMSC-loaded patch promoted the functional maturation of injected hiPSC-CMs. The latter became more elongated, rectangular in cell shape, and appeared more organized—typical morphological characteristics of mature adult CMs. Functional maturation of intramyocardially injected hiPSC-CMs is particularly important because it can reduce potential risk of irregular heart contractions, which is a major cause of sudden cardiac death.
“We believe this novel dual approach can potentially provide translational and clinical benefit to the field of cardiac regeneration,” said Ban. “Based on the same principle, the protocol may also be utilized for repairing other organs including the brain, the liver and the pancreas, in which multiple types of stem cells are co-existing.”
The team is working on follow-up studies in larger animal model such as pigs. A patent application for the technique has been submitted.
The article can be found at: Park et al. (2019) Dual Stem Cell Therapy Synergistically Improves Cardiac Function and Vascular Regeneration Following Myocardial Infarction.
Source: City University of Hong Kong; Photo: Shutterstock.
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