Baltimore, Md., May 22, 2019 - Stem-cell based therapies to strengthen the heart muscle and treat other diseases are beginning to show promise in human clinical trials. However, other than observing clinical outcomes, lack of a repeatable, time-sensitive and noninvasive tool to assess the effectiveness of the transplanted cells within the target organ has slowed progress in the stem cell field.
Researchers from the University of Maryland School of Medicine (UMSOM), the University of Pennsylvania and Emory University theorized that a blood test could be used to track the efficacy of transplanted stem cells. They aimed to achieve their goal by analyzing tiny cellular components called exosomes, secreted from the transplanted stem cells into the recipient blood. They tested their theory in rodent models of heart attack, or myocardial infarction, after transplanting two types of human cardiac stem cells and monitoring their circulating exosomes. The researchers found circulating exosomes delivered cell components to the target heart muscle cells, resulting in cardiac repair. Results are published in the journal Science Translational Medicine.
"Exosomes contain the signals of the cells they're derived from - proteins as well as nucleic acids and micro ribonucleic acids (miRNAs) - which affect receptor cells and remodel or regenerate the organ we're targeting," said study co-senior author Sunjay Kaushal, PhD, MD, Professor of Surgery at UMSOM and Director of Pediatric Cardiac Surgery at the University of Maryland Children's Hospital. "We now have a tool to determine whether stem cell therapy will be efficacious for an individual patient, not only for the heart but for any organ that received stem cell therapy."
Through the blood test, which the researchers call a "liquid biopsy," the researchers monitored human cardiosphere-derived cells (CDCs) and cardiac progenitor cells (CPCs) transplanted into rat hearts following myocardial infarction. Blood plasma concentrations of the exosomes were compared seven days after transplant.
After purifying the CDC/CPC-derived exosomes, the researchers found the exosomes contained miRNAs associated with heart muscle recovery. Further, they found CPCs and CDCs produced in culture differed in contents from exosomes produced by transplanted cells in the living organism.
"Our study should be considered the first stepping stone in understanding what stem cells do, but an important point is that the cells we identified as responding changed their gene expression, behavior and secretions," said co-lead author Sudhish Sharma, PhD, UMSOM Assistant Professor of Surgery. "By using these biomarkers, we can understand the mechanism and extent of recovery."
P. Saha, S. Sharma, L. Korutla, S. R. Datla, F. Shoja-Taheri, R. Mishra, G. E. Bigham, M. Sarkar, D. Morales, G. Bittle, M. Gunasekaran, C. Ambastha, M. Y. Arfat, D. Li, A. Habertheuer, R. Hu, M. O. Platt, P. Yang, M. E. Davis, P. Vallabhajosyula, S. Kaushal. "Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium." Sci. Transl. Med. 11, eaau1168 (2019)
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically-based care for more than 1.2 million patients each year. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit http://www.medschool.umaryland.edu
About the University of Maryland Medical Center
The University of Maryland Medical Center (UMMC) is comprised of two hospitals in Baltimore: an 800-bed teaching hospital - the flagship institution of the 14-hospital University of Maryland Medical System (UMMS) - and a 200-bed community teaching hospital, UMMC Midtown Campus. UMMC is a national and regional referral center for trauma, cancer care, neurosciences, cardiac care, diabetes and endocrinology, women's and children's health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the flagship hospital are faculty physicians of the University of Maryland School of Medicine. At UMMC Midtown Campus, faculty physicians work alongside community physicians to provide patients with the highest quality care. UMMC Midtown Campus was founded in 1881 and is located one mile away from the University Campus hospital. For more information, visit http://www.umm.edu.
Science Translational Medicine