Exosomes: The Insulin of Our Era?
Miller School experts discussed the potential biomarker and therapeutic value of exosomes at an on-campus research retreat.
Initially believed to be a mechanism for cells to “take out the trash,” the latest research in the exosome field indicates that minute, extracellular vesicles released by all living cells have the power to unlock a host of transformative possibilities as markers of disease and successful therapeutics.
The University of Miami Miller School of Medicine community came together for a specialized topic research retreat, with four exosome researchers presenting “Biological and Translational Application of Exosomes,” followed by a panel discussion.
The retreat shared updated information about exosomes with Miller School personnel across all disciplines. Attendees gained perspective on how the untapped potential of exosomes can improve both research and diagnostics.
Interest in Exosomes on the Rise
Joshua Hare, M.D., Louis Lemberg Professor of Medicine in the Division of Cardiovascular Medicine and director of the Interdisciplinary Stem Cell Institute (ISCI) at the Miller School, led off the presentations with “Exosomes: A Therapeutic Mediator for Regenerative Medicine.” He detailed how exosomes participate in extra-cellular communication and crosstalk and serve as mediators of tissue repair, with tunneling nanotubes between cells leading to immediate tissue rejuvenation. Exosomes can also be isolated in large quantities.
Dr. Hare was part of the team that found exosomes improve cardiac function after myocardial infarction.
“Exosomes have become an area of great interest across disciplines over the past 10 years,” said Dr. Hare, who is also director of the Donald Soffer Endowed Program in Regenerative Medicine and chief science officer at the Miller School. “That interest is what has energized me to keep working in this area.”
Dr. Hare said exosomes are effectors for cell-based regenerative therapy and contain RNA species with signaling capability. As such, they have the potential to engineer cargo tailored to specific disease indications.
Human Schwann Cells
Next, W. Dalton Dietrich, Ph.D., scientific director of The Miami Project to Cure Paralysis and professor of neurological surgery, neurology, biomedical engineering and cell biology at the Miller School, discussed the role of exosomes in the diagnosis and treatment of neurological disorders.
He outlined how, following brain injury, extracellular vesicles released from injured cells contain neurotoxic proteins that spread into the bloodstream and potentially damage multiple organ systems such as the lungs, gut and heart. Current fluid biomarker research is evaluating levels of these proteins as indicators of injury severity and the identification of novel therapeutic targets for neuroprotection and repair.
With research spanning the past 25 years, Dr. Dietrich and colleagues have studied the use of human Schwann cell transplantation as a strategy for repairing the injured spinal cord because of their potential to induce axonal regeneration and myelination. Schwann cells are readily accessible, produce growth factors, can be transplanted autologously and are available in large numbers for transplantation. More recently, research strategies have also tested the impact of human, Schwann cell-derived exosomes on the structural and functional consequences of neurotrauma.
The most encouraging developments have come from the systemic delivery of human Schwann cell-derived exosomes after experimental traumatic brain injury. Recently published data show that this experimental treatment reduces harmful inflammatory processes and decreases neuropathological damage.
“Our working hypothesis is that human Schwann cell exosomes hold a rich cargo of proteins, lipids and genetic materials that, when delivered to injured tissues, start protective and reparative processes leading to improved functional recovery,” said Dr. Dietrich, also senior associate dean for team science and co-director of the Institute for Neural Engineering at the Miller School. “Current studies in the laboratory are replicating these exciting findings in other injury models of traumatic brain and spinal cord injury for potential clinical translation. We are also attempting to alter the genetic cargo of the exosomes to target more specific downstream signaling cascade to maximize the beneficial effects on outcome.”
Incredible Potential
Ph.D. candidate Aisha Khan discussed how exosomes can be harnessed for groundbreaking research, diagnostics and therapeutics. In addition to being biomarkers for early disease detection and diagnosis, the hope is that exosomes can be used in the treatment of a wide range of conditions, from pulmonary, cardiovascular, neurological and autoimmune diseases to arthritis, cancer and even diabetes.
“It may be a bold statement, but exosomes could be the insulin of our era—we’ll discover this together,” said Khan, executive director of laboratory operations at the Miller School.
Khan shared her research findings on exosomes and extracellular vesicles derived from both Wharton’s jelly and Schwann cells. Her recent publication demonstrates improved cardiac function following myocardial infarction, research that has helped her secure a UO1 grant from the Regenerative Medicine Innovation Project initiative. Currently, she and her team are conducting small animal studies to determine the optimal dose and regimen of Wharton’s jelly-derived extracellular vesicles and to analyze their cargo. While her latest research focuses on exosome cargo, future studies will aim to deepen our understanding of exosome components, structures and functions.
Targeting Inflammation and Pain in Osteoarthritis
To close out the presentations, Dimitrios Kouroupis, Ph.D., assistant professor in the Department of Orthopaedics’ Division of Sports Medicine at the Miller School, presented “Modification of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Cargo: Potential Implications for Inflammation and Pain Reversal.” Based on their research, Dr. Kouroupis and his team proposed mesenchymal stem/stromal cells (MSC) and MSC-derived exosomes (MSC-EXOs) are potent alternatives for inflammation and pain osteoarthritis therapeutics.
The research revealed that modified MSC-EXOs effectively degraded neuropeptide Substance P (SP) and inhibited calcitonin gene-related peptide (CGRP), providing a positive effect on joint inflammation and pain. The team also analyzed 166 MSC-related micro-RNAs and found 147 micro-RNA cargos were present, with 19 highly present. These distinct micro-RNAs regulate genes involved in immunomodulation (such as production of cytokines, the recruitment of monocytes) and anabolic effects (cartilage homeostasis).
On this basis, seven micro-RNAs were previously identified to have significant anti-inflammatory effects. Dr. Kouroupis’ research suggests that yielded exosomes can target both SP and CGRP which are the causes of osteoarthritic neuroinflammatory pain.
“I see lots of potential for PO1 here,” said Dr. Kouroupis. “You can go from manufactured doses to treatment doses and we have already identified investigators, so there’s great potential for very solid PO1.”
The researchers closed out the retreat with a panel discussion, answering questions from their colleagues that illustrated the trajectory of exosomes from “trash can” to potential gold mine. As the scientific community becomes more aware of the power of exosomes, the possibilities for medical applications will continue to expand.
Tags: Aisha Khan, Cardiovascular Division, Department of Orthopaedics, Dr. Dimitrios Kouroupis, Dr. Joshua Hare, Dr. W. Dalton Dietrich III, exosomes, neurological surgery, The Miami Project to Cure Paralysis