The Role of Inflammation

Despite appearing unrelated at first glance, treatments for neurological disorders have provided insights that could inform potential therapies for COVID-19. For instance, cell-based treatments have demonstrated positive outcomes in stroke recovery, which occurs when blood flow to the brain is compromised.

“Research suggests that there’s a systemic, blood-related inflammation, with mechanisms that may resemble those following a brain injury,” notes Benjamin Buller from Oakland University. In response to the pandemic, Buller and his team have redirected their focus towards assessing how similar stem cell therapies could assist COVID-19 patients. “Early reports of increased thrombosis and D-dimer levels in COVID patients caught my attention,” he explained during a recent webinar on regenerative medicine approaches to combat the virus.

The common thread linking strokes and COVID-19 is inflammation. In both scenarios, pro-inflammatory substances flood tissues, leading to hyperactive immune responses and triggering blood clotting. Infection with SARS-CoV-2 provokes a widespread inflammatory reaction, which can lead to acute respiratory distress syndrome (ARDS). This condition causes fluid to build up in the lungs’ alveoli—tiny air sacs responsible for oxygen absorption. Once ARDS reaches a critical phase, approximately 40% of patients face fatal outcomes.

Clinical markers observed in brain trauma bear similarities to those in ARDS, implying that MSC-based treatments could also be beneficial for severe COVID-19 cases. “This indicates a systemic, blood-based inflammatory response, akin to what occurs following a brain injury,” Buller elaborates.

The Discovery of Exosomes

In initial preclinical trials, Buller and his colleagues made remarkable discoveries when MSCs were applied to damaged brain tissues: the stem cells transformed into neurons, enabling recovery through tissue remodeling and neural circuitry reconfiguration. Subsequent studies revealed that the source of these potent regenerative effects lay in tiny "bubbles" released by stem cells, containing a wealth of regenerative agents. Known as extracellular vesicles or exosomes, these membrane-bound structures transport various proteins, lipids, and nucleic acids, facilitating cell communication. In animal stroke models, purified exosomes yielded impressive outcomes, replicating the benefits of stem cell grafts and significantly enhancing cognitive and behavioral recovery.

Breathing Easier with MSCs

These findings have paved the way for exploring exosomes in treating other inflammatory diseases. Although still in preliminary stages, results from testing this theory in COVID-19 are promising. Earlier this year, a small study indicated that seven COVID patients who received intravenous MSC injections exhibited significant improvements in their recovery from ARDS.

“MSCs can mitigate inflammation, preventing it from becoming too severe, while simultaneously enhancing the immune response to eliminate pathogens and facilitate organ healing,” Buller explains.

Interest in stem cells for ARDS has surged, with multiple clinical trials underway to evaluate the safety and effectiveness of these therapies. One such effort is the CIRCA-19 trial, which focuses on cellular immunotherapy for ARDS related to COVID-19, sponsored by the Ottawa Hospital Research Institute. Duncan Stewart, CEO and Scientific Director of the Institute, believes that stem cells may help patients recover from COVID through various mechanisms, asserting, “MSCs can reduce inflammation while supporting the immune system’s ability to clear pathogens and promote healing.”

Exosomes are also being examined for their potential use as a delivery platform for COVID vaccines and medications to the lungs. These particles can be loaded with nucleic acids encoding a vaccine or antibody against the SARS-CoV-2 virus, potentially overcoming limitations posed by synthetic drug carriers. In the future, exosomes could be administered to patients as aerosol sprays, rather than through injections or IV infusions.

Navigating the Challenges Ahead

As with any emerging treatment, the journey from research to clinical application is fraught with obstacles. While MSCs and exosomes have demonstrated their potential in controlled experimental settings, regulatory agencies require a host of criteria to be met before they can be utilized in clinical practice. Developers must guarantee the purity and effectiveness of each treatment dose—a complex challenge given the inherent variability of MSCs derived from different donors. The stem cell research community is advocating for more stringent testing and validation processes to ensure that MSCs and exosomes can become viable frontline therapies for COVID-19.

Experts caution that no single treatment—whether a vaccine, medication, or cell therapy—will likely serve as a cure-all. The full impact of various therapeutic options remains uncertain, especially since much is still unknown about this formidable viral threat. However, one thing is evident: the robust ecosystem of stem cell research and development has laid a strong foundation for the dedicated scientists striving to create the COVID treatments of tomorrow.

For further insights into the challenges and opportunities in regenerative medicine as we navigate the aftermath of COVID-19, check out Signal’s fifth annual blog carnival here.