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Preclinical Study Suggests That Nanowired Cardiac Organoids Could One Day Repair Hearts Instead of Just Preventing Further Damage
A team of bioengineers and clinician-scientists at the Medical University of South Carolina (MUSC) and Clemson University (CU) are on the cusp of a revolutionary approach that could change the landscape of cardiac care by repairing damaged heart tissue. They reported their promising preclinical findings in the August issue of Science Advances. The team is led by Ying Mei, Ph.D., who has a joint appointment at CU and MUSC and is part of the CU-MUSC program in Bioengineering. Ryan Barrs, a doctoral candidate in the joint program, is one of the lead authors of the article.
“The damage left behind by heart attacks is usually thought to be permanent and can require heart transplants, which are in short supply,” said Barrs. “Here, we developed electrically conductive ‘mini-hearts’ that could be injected into injured heart muscle to restore its pumping function.”
Courtesy Medical University of South Carolina, Ryan Barrs
Many researchers have tried to crack the puzzle of how to help the heart to repair itself. One promising strategy for replenishing dead heart cells and promoting repair was individual stem cells that could be differentiated into 'repair-promoting' heart tissue. However, this approach fell short.
To understand why, picture the chaotic environment inside a heart after an attack – a landscape rife with inflamed tissue and a relentless pumping that gives no quarter to new cells. Adding individual stem cells is akin to planting a delicate sapling in the middle of a storm; the chances of it taking root are slim, said Mei.
"The heart would often squeeze the stem cells into the blood vessels, causing potential side effects and inefficiencies," explained Mei. "Moreover, the single cells face a hostile environment in the heart, especially after a heart attack, reducing their survival and effectiveness."
Mei and his interdisciplinary team produced a new strategy that addresses the weaknesses of past approaches. They have developed a more resilient cellular structure to surround the stem-cell derived heart cells called cardiac organoids. Think of them as tightly knit clusters of structural cells that are more likely to withstand the heart's challenging environment.
"By making these cells into small heart-like microtissues, we can create a more sustainable and resistant structure, capable of withstanding the sudden change of environment," said Mei.
To assess the ability of the organoids to heal damaged hearts in a preclinical model, Mei collaborated with experts in cell therapy and heart disease at MUSC, including Hongjun Wang, Ph.D., Kristine DeLeon-Pennell, Ph.D., and Donald Menick, Ph.D.
In this animal study, injecting these cardiac organoids directly into the heart led to a 39% recovery of the function lost due to a simulated heart attack. This finding suggests that the cell device goes beyond mere prevention of further damage and contributes to repair of already damaged tissue.
The interdisciplinary team was still not satisfied and wanted to take things a step further.
"We realized that another layer of engineering was needed to ensure proper integration with the host tissue," Mei said.
Thus, the idea of electrically conductive silicon nanowires was born. These tiny biocompatible wires, invisible to the naked eye, enhance the organoids, synchronizing them with the native heart's electrical signals. The electrical signals help the clustered cells to move in unison, making them more effective at integrating and pumping with the existing heart tissue.
The result? An astonishing 69% increase in heart function.
Nanowired human cardiac organoids could represent a leap forward in cardiac care because they go beyond merely preventing further heart damage to actively repairing the damage already done.
"Our study is the first to show in a preclinical model that this combination of nanotechnology and organoid technology holds promise for repairing tissue damage after a heart attack," said Mei.
The team is now focused on enhancing and refining this technique. “First, we plan to investigate more closely how the nanowires improve cardiac organoid therapy,” said Barrs. Further research, testing and validations will also be needed to make this method a clinical reality. If that research continues to show the promise of this novel approach, Mei hopes it will be tested in clinical trials in the next decade.
“Our ultimate goal is to provide a more effective and accessible therapy than a heart transplant to heal injured hearts,” said Mei.
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'About MUSC
Founded in 1824 in Charleston, MUSC is the state’s only comprehensive academic health system, with a unique mission to preserve and optimize human life in South Carolina through education, research and patient care. Each year, MUSC educates more than 3,200 students in six colleges – Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy – and trains more than 900 residents and fellows in its health system. MUSC brought in more than $298 million in research funds in fiscal year 2022, leading the state overall in research funding. MUSC also leads the state in federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.
As the health care system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest-quality and safest patient care while educating and training generations of outstanding health care providers and leaders to serve the people of South Carolina and beyond. Patient care is provided at 16 hospitals (includes owned and equity stake), with approximately 2,700 beds and four additional hospital locations in development; more than 350 telehealth sites and connectivity to patients’ homes; and nearly 750 care locations situated in all regions of South Carolina. In 2022, for the eighth consecutive year, U.S. News & World Report named MUSC Health University Medical Center in Charleston the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.
MUSC has a total enterprise annual operating budget of $5.1 billion. The nearly 26,000 MUSC family members include world-class faculty, physicians, specialty providers, scientists, students, affiliates and care team members who deliver groundbreaking education, research, and patient care.
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