UCSF Investigates Regenerative Cellular Therapies Targeting Often Fatal COVID-19 ARDS

UCSF Investigates Regenerative Cellular Therapies Targeting Often Fatal COVID-19 ARDS

Researchers from the University of California, San Francisco (UCSF) launched a study back in January to investigate the regenerative powers of mesenchymal stem cells (MSCs) but at the onset of the COVID-19 and with the approval of regulators, the research team pivoted to investigate whether cells derived from deep within the human bone can ultimately aid patients with a severe form of SARS-CoV-2, the virus behind COVID-19—that is those afflicted with acute respiratory distress syndrome (ARDS). Led by Michael Matthay, MD, UCSF conducts an ongoing randomized, double blind clinical trial assessing the efficacy and safety of mesenchymal stem cells (MSCs) for patients with ARDS. The Phase 2 study, funded by the Department of Defense, the National Institutes of Health (NIH) and the California Institute of Regenerative Medicine (CIRM), targets 120 ARDS patients. These patients are in danger, in the ICU and on ventilators.

ARDS: A Very Dangerous Situation

Severe progression of COVID-19 can lead to ARDS, a dangerous condition with a mortality rate of 27 percent for mild cases and 45 percent for severe ones. One study referred to in the recent UCSF news suggests only a 25 percent survival rate for those COVID-19 patients with ARDS. Dr. Matthay reminds that figure can hover at 40 percent. This is one reason why the United States has lost so many lives.

Referring to the condition, UCSF principal investigator Dr. Matthay commented about ARDS, “tiny air spaces in the lungs will up with fluid and prevent normal oxygen update in the lungs.” He continued, “That’s why the patient has respiratory failure. Usually these patients have to be intubated and treated with a mechanical ventilator.”

An ongoing study at UCSF, Zuckerberg San Francisco General Hospital and soon UC Davis as well as four other sites reports Jen A. Miller writing for UCSF, the study team and sponsor home that the MSC-based regenerative therapy can heal the severe the ARDS.

Mesenchymal Stem Cells

Ms. Miller introduces the reader to the bone marrow born MSC, stromal cells that actually play a regenerative role in the body, helping to repair skeletal tissues (e.g. bone, cartilage, etc.). More specifically, MSCs are adult stem cells isolated from different sources  that can transform into other types of cells. In humans these sources include; bone marrow, fat (adipose tissue), umbilical cord tissue (Wharton’s Jelly) or amniotic fluid.

These cells have the ability to differentiate into different types of cells including bone cells, cartilage, muscle cells, neural cells, liver and perhaps even the lungs. MSCs are mostly found in the bone marrow of humans and are dormant till triggered for regenerative missions within the body. As the human ages, so do the cells and their number and effectiveness decrease over time.

Hypothesis to Address COVID-19 & ARDS

Researchers actually discovered that when MSCs are transplanted in humans they can modulate inflammation. Hence the interest in investigating other possible therapeutic areas for use such as COVID-19-based ARDS.

A search in the government-funded Clinicaltrials.gov clinical trials database reveals at least 51 clinical trials, involving COVID-19 and MSC-based regenerative therapy.

Although this investigational regenerative therapy represents promise UCSF’s Dr. Matthay suggests it’s the early days noting “We’re really in the early phases of understanding these cell-based therapies.”

Matthay and team have conducted early stage research and, according to UCSF’s news, demonstrated safety with MSC use. However there is so little known: how effective will MSC infusions really be? Will the results differ depending on the cause of ARDS? What complementary treatments would have maximum efficacy? 

As there is significant “heterogeneity” behind ARDS syndrome, its “mechanisms of injury to the lung and also outcomes” investigators are now testing various scenarios on COVID-19 patients to learn more and hopefully produce the evidence to progress the research.

The Study

Originally set up to investigate MSC regenerative properties as applied to lung injury, now the Phase 2 double blind study, funded by a combination of the Department of Defense, NIH and CIRM, targets 120 ARDS patients. By the end of August 28th, patients were enrolled in this study. The actual MSCs used for the study were donated by a group of young, healthy adults from the NIH-supported cell laboratory at the University of Minnesota.

Other MSC Studies Targeting COVID/ARDS

TrialSite reported that there are at least 51 clinical trials around the world investigating the efficacy and safety of MSCs to patients with severe COVID-19 progression, including ARDSs. Companies have emerged in an attempt to commercialize regenerative therapies but they first must prove that their investigational therapies actually work.


For example, Mesoblast is developing a proprietary regenerative technology platform based on innovative allogeneic cellular medicines to treat complex diseases resistant to the typical standard of care and where inflammation plays a central role. One of their products, RYONCIL (remestemcel-L) was developed for steroid-refractory acute graft versus host disease (acute GVHD), as well as treatment of moderate to severe acute respiratory syndrome (ARDS) due to COVID-19 infection.

The company received an accepted priority review by the U.S. Food and Drug Administration for their Biologics License Application (BLA) to seek approval for acute GVHD in children. The investigational product could be approved as soon as the end of September.

Mesoblast in collaboration with Icahn School of Medicine at Mount Sinai conducts a Phase 3 clinical trial (NCT-4371393) investigating the efficacy and safety of the addition of MSC remestemcel-L plus standard of care as compared to placebo plus standard of care in patients with ARDS due to COVID-19. The sponsors also seek to assess the impact of MSCs on inflammatory biomarkers. This study was initiated in April 2020 and its estimated primary completion date is April 2021.


Balyx, touting “stem cell innovation” focuses on the development and manufacturing of “off-the-shelf” Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSC) from “medical waste.” Led by Vincent Liao, this Orange County, CA company is conducting an open-label, single-arm, dose-escalating study (NCT04452097) to evaluate and explore the dose limiting toxicity and maximum tolerated dose of human umbilical cord derived MSC (BX-U001) in severe COVID-19 pneumonia patients with ARDS.


Houston-based Celltex received FDA approval back in late June to commence with a clinical trial targeting COVID-19 to investigate the prophylactic efficacy of autologous adipose tissue-derived mesenchymal stem cells (AdMSCs).  Founded in 2011, Celltex has raised $34.1 million

Cartesian Therapeutics

Founded in 2016, Gaithersburg, MD-based Cartesian Therapeutics is a fully integrated clinical-stage biopharmaceutical venture developing novel cell and gene immunotherapies to treat cancer and autoimmune disease. The company prepares to launch a Phase 1/2 clinical trial (NCT04524962) in mid-September. The sponsor investigates the safety of Descartes-30 cells, derived from allogeneic MSCs engineered to express DNases, in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. According to Pitchbook, the company has raised $7.2 million in two investment rounds.

University of Miami

The use of MSCs to combat COVID-19 raises different perspectives and points of view. In a Chinese study, seven COVID-19 patients received intravenous infusions of donor MSCs. The results evidenced overall safety and that their results may improve patient outcomes. Despite that, scientists are not in alignment with the logic behind this method and how well MSCs performed in this pilot study. TrialSite News reported on the FDA approval of Mesoblast’s IND for an MSC-based product. The study was premised on the fact that their investigational product remestemcel-L was successful in a Phase 3 clinical trial for steroid-refractory acute graft versus host disease (aGVHD) in children—a potentially fatally inflammatory condition due to a similar cytokine storm process as seen in COVID-19 acute respiratory distress syndrome. In May, the company reported that the first patients were dosed in the 300-patient randomized placebo-controlled Phase 2/3 trial in the United States of Mesoblast’s allogeneic cellular medicine remestemcel-L.

Lead Research/Investigator (UCSF)

Michael Matthay, MD Professor of Medicine

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