Study looked at the treatment of severe COVID-19 with mesenchymal stem cells derived by umbilical cord.
The researchers at the University of Miami Miller School of Medicine conducted a unique and groundbreaking, randomized, controlled trial that shows that mesenchymal stem cell infusions are safely reduced by umbilical cords and reduce recovery time for the most severe COVID-19 patients. according to the results published in STEM SYSTEMS Translational Medicine in January 2021.
The senior author of the study, Camillo Ricordi, MD, director of the Diabetes Research Institute (DRI) and the Cell Transplant Center at the University of Miami Miller School of Medicine, said that treating COVID-19 with mesenchymal stem cells makes sense.
Results: treatment group versus control group
The article describes findings from 24 patients hospitalized at the University of Miami Tower or Jackson Memorial Hospital with COVID-19, who developed severe acute respiratory distress syndrome. Each received two administrations, with separate days of mesenchymal stem cells or placebo.
“It was a double-blind study. “Doctors and patients did not know what was administered,” said Dr. Ricordi said. “Two infusions of 100 million stem cells were delivered within three days, for a total of 200 million cells in each subject in the treatment group.”
Researchers found that the treatment was safe, with no infusion-related serious side effects.
The patient’s survival at one month was 91% in the stem cell treated group versus 42% in the control group. Among patients under 85 years of age, 100% of those treated with mesenchymal stem cells survived one month.
Dr Ricordi and colleagues also found that the time in treatment was faster to recover. More than half of the patients treated with mesenchymal stem cell infusions recovered and were discharged from the hospital within two weeks of the last treatment. More than 80% of the treatment group recovered on day 30, compared to less than 37% in the control group.
“The umbilical cord contains progenitor cells, or mesenchymal stem cells, which can be expanded and provide therapeutic doses for more than 10,000 patients from one umbilical cord. ‘It is a unique source of cells that are being investigated for its possible use in cell therapy applications, whenever you need to modulate the immune response or inflammatory response,’ ‘he said. “We have been studying this with our collaborators in China for over ten years on type 1 diabetes, and there are currently more than 260 clinical studies listed in clinicaltrials.gov for the treatment of other autoimmune diseases.”
Mesenchymal stem cells can restore the normal immune response
Mesenchymal cells not only help to correct immune and inflammatory reactions that go wrong, but they also have antimicrobial activity and show that it promotes tissue regeneration.
“Our results confirm the potent anti-inflammatory, immunomodulatory effect of UC-MSC. These cells clearly inhibited the ‘cytokine storm’, a characteristic of severe COVID-19, ‘said Giacomo Lanzoni, MD, lead author of the article and assistant research professor at the Diabetes Research Institute. “The results are important not only for COVID-19 but also for other diseases characterized by aberrant and hyperinflammatory immune responses, such as autoimmune type 1 diabetes.”
When administered intravenously, mesenchymal stem cells naturally migrate to the lungs. This is where therapy is needed in COVID-19 patients with acute respiratory distress syndrome, a dangerous complication associated with severe inflammation and fluid buildup in the lungs.
“It seemed to me that these stem cells could be an ideal treatment option for severe COVID-19,” said Dr. Ricordi, professor Stacy Joy Goodman in surgery, leading professor of medicine, and professor of biomedical engineering, microbiology and immunology said. ‘It requires only an intravenous (IV) infusion, such as a blood transfusion. It is like smart bomb technology in the lung to restore the normal immune response and prevent life-threatening complications. ”
Early success with mesenchymal stem cells
When the pandemic broke out, dr. Ricordi colleagues in China asked if they had studied mesenchymal stem cell treatment in COVID-19 patients. In fact, they and Israeli researchers have reported great success in treating COVID-19 patients with the stem cells, in many cases with 100% of the treated patients surviving and recovering faster than those without stem cell treatment.
However, there was widespread skepticism about these initial results, as none of the studies were randomized, where patients received randomized treatment or a control solution (placebo) to compare the results in similar groups of patients.
“We approached the FDA and they approved our proposed randomized controlled trial within one week, and we started as soon as possible,” said Dr. Ricordi said.
Dr. Ricordi collaborates with several key collaborators at Miller School, the University of Miami Health System, Jackson Health System, and collaborates with others in the U.S. and internationally, including Arnold I. Caplan, Ph.D., of Case Western Reserve University, which first described mesenchymal stem cells.
The next step is to study the use of the stem cells in COVID-19 patients who have not yet become seriously ill, but are at risk of being intubated, to determine whether the infusions can prevent the progression of the disease.
According to Dr Ricordi, the findings also have implications for studies related to other diseases.
Hyper-immune and hyper-inflammatory responses in autoimmune diseases may be a common thread as to why some COVID-19 patients switch to severe forms of the disease and others do not.
“Auto-immunity is a major challenge for healthcare, just like COVID-19. Autoimmunity affects 20% of the U.S. population and contains more than 100 disease states, of which type 1 diabetes can only become the tip of the iceberg. What we are learning is that there may be a common thread and there may be risk factors for an autoimmune disease or for a severe reaction to viral infections, such as EARS-CoV-2, “he said.
The DRI Cell Transplant Center plans to create a large repository of mesenchymal stem cells that are ready to use and can be distributed to hospitals and centers in North America.
“It can be used not only for COVID-19, but also for clinical trials for the treatment of autoimmune diseases, such as type 1 diabetes,” said Dr. Ricordi said. ‘If we can induce these cells at the onset of type 1 diabetes, we can block the progression of autoimmunity in newly diagnosed subjects, and the progression of complications in patients affected by the disease in the long term. We are planning such a trial specifically for diabetic nephropathy, a kidney disease that is one of the leading causes of dialysis and kidney transplantation. We also plan to conduct a study on umbilical cord mesenchymal stem cell transplantation in combination with pancreatic islets to see if you can modulate the immune response to an islet transplant locally. ”
Funding by The Cure Alliance made it possible to launch the initial trial, while a $ 3 million grant from North America’s Building Trades Unions (NABTU) Dr. Ricordi and colleagues were able to complete the clinical trial and expand research with mesenchymal stem cells.
North America’s Building Trades Unions (NABTU) have been a major proponent of the Diabetes Research Institute since 1984, when they launched a campaign to fund and build our modern research and treatment facility. “NABTU has continued to support our work over the years, including our mesenchymal stem cell research that led the way to this clinical trial,” he said.
Reference: January 5, 2021, STEM SYSTEMS Translational Medicine.
All of the organizations that fund the research are nonprofits, including the Barilla Group and Family, The Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, and the Diabetes Research Institute Foundation. The National Center for the Advancement of Translation Sciences has also provided funding.
Co-authors on the NEJM article include: Giacomo Lanzoni, Ph.D., Assistant Research Professor, DRI; Elina Linetsky, Ph.D., DRI Director of Quality Assurance and Regulatory Affairs; Diego Correa, MD, Ph.D., Assistant Professor (Research) Dept of Orthopedics and the DRI, Deputy Assistant Professor of Biology at Case Western Reserve University; Shari Messinger Cayetano, Ph.D., Associate Professor of Public Health Sciences at Miller School; Roger A. Alvarez, DO, MPH, a pulmonologist with UHealth Pulmonary and Sleep Medicine; Antonio C Marttos, MD, a general surgeon at UHealth; Ana Alvarez Gil, DRI; Raffaella Poggioli, MD, DRI; Phillip Ruiz, MD, Ph.D., Department of Surgery at Miller School and the Division of UHealth Anatomic Pathology; Khemraj Hirani, M.Pharm., Ph.D., R.Ph., CCRP, CIP, RAC, MBA, Director of Regulatory Affairs and Quality Assurance at the DRI; Crystal A. Bell, Department of Medicine at Miller School; Halina Kusack, Department of Medicine, Miller School; Lisa Rafkin, Research Assistant Professor, DRI; Rodolfo Alejandro, managing director, professor of medicine at the Miller School, co-director of the Cell Transplant Center, and director / treating physician of the Clinical Cell Transplant Program at the DRI; David Baidal, MD, Assistant Professor of Medicine in the Department of Endocrinology, Diabetes and Metabolism at Miller School and member of the DRI’s clinical island transplant program; Andrew Pastewski, Managing Director, Jackson Health System; Kunal Gawri, Miller School and the University of Miami Health System; Dimitrios Kouroupis, postdoctoral research fellow at Miller School; Clarissa Leñero, DRI; Alejandro MA Mantero, Ph.D., Chief Research Analyst, Department of Health Sciences at Miller School; Xiaojing Wang, DRI; Luis Roque, DRI; Burlett Masters, DRI; Norma S. Kenyon, Ph.D., Deputy Director and Martin Kleiman Professor of Surgery, Microbiology and Immunology and Biomedical Engineering at the DRI; Enrique Ginzburg, MD, chief of surgery at the University of Miami Hospital and medical director of trauma at Jackson South Community Hospital; Xiumin Xu, DRI; Jianming Tan, MD, Ph.D., Fuzhou General Hospital, Fujian, China; Arnold I. Caplan, Ph.D., professor of biology at Case Western Reserve University; and Marilyn Glassberg, MD, Head of Pulmonary Medicine, Critical Care and Sleep Medicine at the University of Arizona College of Medicine.