Evaluating EVs

DURHAM, N.C.—A team of researchers at the University of Duisburg-Essen have found a potential new approach to aid the brain in recovering from a stroke—one that already exists in the body. The results were published in STEM CELLS Translational Medicine in a paper titled “Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Post-Ischemic Immunosuppression.” The team consisted of 10 scientists from Duisburg-Essen’s Department of Neurology and Institute for Transfusion Medicine, and the study received support from the University, Volkswagen Foundation and German Research Council.

Extracellular vesicles (EVs) are tiny membrane-enclosed structures that travel between cells. These tiny bodies are thought to transmit biological signals between cells to direct a wide range of processes, and given their biological function, are under scrutiny for what role they might play in conditions such as neurological disorders, cancer and infectious diseases. As noted in the paper's abstract, “Although the initial concepts of stem cell therapy aimed at replacing lost tissue, more recent evidence has suggested that stem and progenitor cells alike promote postischemic neurological recovery by secreted factors that restore the injured brain’s capacity to reshape. Specifically, extracellular vesicles (EVs) derived from stem cells such as exosomes have recently been suggested to mediate restorative stem cell effects.”

In this study, EVs derived from mesenchymal stem cells (MSC) were administered to a group of stroke-impaired mice, while a second group received adult stem cells from bone marrow. The team monitored coordination deficits, histological brain injury, immune responses in the peripheral blood and brain and cerebral angiogenesis and neurogenesis. After four weeks of monitoring, both sets of mice had experienced the same degree of neurological repair. Furthermore, in addition to promoting brain recovery, EVs also seemed to modulate post-stroke immune responses and offer long-term neurological protection, with the paper noting that “Although cerebral immune cell infiltration was not affected by MSC-EVs, post-ischemic immunosuppression (i.e., B-cell, natural killer cell, and T-cell lymphopenia) was attenuated in the peripheral blood at six days after ischemia, providing an appropriate external milieu for successful brain remodeling.”

Team co-leaders Thorsten Doeppner, a neurologist, and Bernd Giebel, a transfusion medicine specialist, pointed out that EVs have fewer risks than adult stem cell transplants, adding that “The fact that intravenous EV delivery alone was enough to protect the post-stroke brain and help it recover highlights the clinical potential of EVs in future stroke treatment.”

“We predict that with stringent proof-of-concept strategies, it might be possible to translate MSC-EV therapy from rodents to human patients, because MSC-EVs are more suitable for clinical application than is transplantation of (undifferentiated) stem cells,” the authors noted in the paper.

“The current research, combined with the previous demonstration that EVs are well tolerated in men, suggests the potential for using this treatment in conjunction with clot-busting therapies for treatment of stroke,” remarked Dr. Anthony Atala, editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.