New research from the University of Wisconsin–Madison and Mayo Clinic shows promising results in using stem cell technology to repair damaged heart muscle in monkeys, a breakthrough that could have significant implications for treating congenital heart defects in humans. This research, led by Professor Marina Emborg from the UW–Madison School of Medicine and Public Health and Dr. Timothy Nelson, a physician-scientist at the Mayo Clinic, was published in the journal Cell Transplantation. Their study focuses on the use of heart muscle cells derived from induced pluripotent stem cells (iPSCs) to treat right ventricular dysfunction, a condition often caused by congenital heart defects.
Congenital heart defects are structural problems with the heart that are present at birth. These conditions can lead to severe health issues, including pressure overload in the right ventricle. This pressure overload occurs when the heart has to work harder to pump blood, eventually leading to right ventricular dysfunction. Symptoms include chest discomfort, difficulty breathing, irregular heartbeats, and swelling, and if untreated, it can result in heart failure. Right ventricular dysfunction is particularly challenging to manage because nearly all single ventricle congenital heart defects—especially those affecting the right side of the heart—progress toward heart failure over time. While surgical repairs can temporarily alleviate the condition, they are not a permanent solution, and many patients eventually face the need for a heart transplant.
However, heart transplantation is not always feasible, especially for children. The demand for donor hearts far exceeds the supply, particularly for young patients who often require a transplant at an early age. This shortage underscores the importance of exploring alternatives to traditional heart transplants, a gap that stem cell research aims to fill.
The study conducted by Emborg, Nelson, and their team investigates the potential of using stem cell-derived cardiomyocytes, specialized heart muscle cells, as a supplementary treatment to conventional surgery. These cardiomyocytes were developed from clinical-grade human iPSCs. Induced pluripotent stem cells are adult cells, often taken from blood or skin, that have been reprogrammed to a stem cell state, allowing them to differentiate into various cell types, including heart muscle cells. The researchers then transplanted these lab-grown cardiomyocytes into rhesus macaque monkeys, which had been surgically modified to develop a condition mimicking human right ventricular pressure overload.
Once transplanted, the stem cell-derived heart cells successfully integrated into the monkeys’ heart tissue. The new cells not only became part of the existing myocardium—the thick muscular layer of the heart—but also began to contribute to heart function. Throughout the study, the researchers closely monitored the health and cardiac function of the monkeys to evaluate how well the transplanted cells were assimilating with the native heart tissue.
The research team reported a few challenges, particularly episodes of ventricular tachycardia—a condition characterized by an abnormally high heart rate—in five out of the 16 monkeys that received the transplanted cells. Two of these animals experienced persistent tachycardia, but the condition resolved itself in all cases within 19 days. These findings highlight the complexity of integrating lab-grown cells into a living heart and underline the need for further studies to refine the process.
Despite these challenges, the successful integration of the cells marks a significant milestone. According to Jodi Scholz, the study’s lead author and Chair of Comparative Medicine at the Mayo Clinic, stem cell therapy holds promise as a method to delay or even prevent the need for heart transplants. “There is a great need for alternative treatments of this condition,” Scholz said. “Stem cell treatments could someday delay or even prevent the need for heart transplants.” If stem cells can be effectively used to support the heart’s structure and function, they may provide a longer-term solution that reduces or eliminates the dependency on donor hearts.
This study is especially groundbreaking because it represents the first successful use of stem cells in a nonhuman primate model of right ventricular pressure overload. The choice of rhesus macaque monkeys was intentional, as they share physiological similarities with humans, making them an ideal model for studying the safety and effectiveness of new therapies before transitioning to human trials. The study also builds on previous stem cell research targeting conditions like Parkinson’s disease and kidney disease, showing that advances in one area of medicine can inform and enhance research in others.
Professor Emborg, who has extensive experience in stem cell research, particularly in neurological disorders like Parkinson’s, emphasized that the primary objective of this study was to ensure the safety and proper integration of the stem cells. “Our goal with this particular study, as a precursor to human studies, was to make sure that the transplanted cells were safe and would successfully integrate with the organization of the surrounding tissue,” she explained. This foundational research aims to set the stage for clinical trials involving humans, with the ultimate goal of using stem cells to treat congenital heart defects.
The success of this study has implications beyond congenital heart defects. It demonstrates the broader potential of stem cell therapies in regenerative medicine, a field that seeks to repair or replace damaged tissues and organs. In the context of heart disease, which remains the leading cause of death in the United States, regenerative approaches could provide more effective and less invasive treatments. Instead of relying solely on mechanical devices or surgical interventions, future therapies may harness the body’s own biology to restore heart function.
The researchers are hopeful that continued advances in stem cell technology will lead to more refined and targeted treatments. Emborg views this study as a stepping stone toward future clinical applications: “The demonstration of successful integration and maturation of the cells into a compromised heart is a promising step towards the clinical application for congenital heart defects.” These findings bring the medical community closer to developing new regenerative therapies that could revolutionize the way heart disease is treated.
Source: University of Wisconsin-Madison