New Research: human mesenchymal stem cells treatment for severe COVID-19
Recently, the team of academician Wang Fusheng, director of the Center for Diagnosis and Treatment of Infectious Diseases at the Fifth Medical Center of the PLA General Hospital and director of the National Clinical Research Center for Infectious Diseases, announced the use of human umbilical cord mesenchymal stem cells (UC-MSCs) to treat patients with severe COVID-19 follow-up The results of 1 year, the article was published in the "Lancet" sub-journal - EBioMedicine. There has been no previous report on the long-term follow-up data of UC-MSCs in the treatment of COVID-19 patients at home and abroad. The results showed that UC-MSCs administration had long-term benefits on the recovery of pulmonary lesions and symptoms in COVID-19 patients.
The study prospectively followed up 100 patients previously enrolled in a phase II clinical trial at 3-month intervals for 1 year to assess the long-term safety and efficacy of UC-MSCs treatment. The primary endpoint was the change in percent volume of whole lung lesions detected using high-resolution CT, and other imaging-reported outcomes, 6-minute walk distance (6-MWD), lung function, plasma biomarkers, and adverse events were recorded and analyzed.
It is worth mentioning that the data of this study was classified as the highest 1a by the Oxford evidence level of Oxford University, and the GRADE evidence level was classified as high-level evidence, and was published in November. Quoted in a review in Regenerative Medicine, a sub-journal of Nature.
Mesenchymal stem cells treat severe COVID-19 patients with very positive Long-term follow-up data
Since the outbreak of the new crown epidemic in 2019, the number of confirmed cases worldwide has continued to rise. As of April 1, 2022, there have been more than 488.7 million confirmed cases worldwide. With widespread vaccination and the use of neutralizing antibodies, mortality and hospitalization rates have been greatly reduced. But if there is transmission, there will be mutations. In the era of the global village, a particularly strong mutant strain in any country may occupy the whole world, such as Alpha from the United Kingdom, Delta from India, and Omicron found in South Africa. Even today the XE variant.
It can be seen that compared to the original strain, Delta has 9 mutations distributed on the spike, while Omicron has a dense 34, and many of them are on the surface where the spike protein and the antibody bind (red dots). Therefore, it is inevitable that the protective effect of the vaccine will decrease and the neutralizing antibody drug will fail.
The new coronavirus can severely damage the lungs, ranging from mild respiratory illness to severe acute respiratory syndrome and even death. The current treatment methods for hospitalized patients are mainly supportive therapy, antiviral therapy, and antibacterial therapy. For patients who meet the indications, immunotherapy can also be considered.
In recent years, mesenchymal stem cells have been widely used in the treatment of lung diseases. A number of preclinical studies have confirmed that mesenchymal stem cells have the potential to treat acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The study found that human umbilical cord mesenchymal stem cells have a significant repair effect on the alveolar fluid clearance and protein permeability of H5N1-infected human alveolar epithelial cells. In addition, mesenchymal stem cell exosomes can reduce viral replication through RNA transfer, Reduce the death of alveolar epithelial cells and relieve the symptoms of acute respiratory distress syndrome caused by influenza virus.
Since 2020, a number of clinical trials using various types of MSCs as treatment methods for COVID-19 patients have been launched at home and abroad. The results showed that MSCs not only significantly reduced the lung injury and the recovery time of the patients, but also improved the survival rate of the patients with good early tolerance.
Previously, a double-blind, randomized, placebo-controlled phase II clinical trial of UC-MSCs in the treatment of severe COVID-19 patients conducted by Academician Wang's team included a total of 100 patients. In addition to receiving standard care, patients were divided into groups receiving UC-MSCs (n = 65) and placebo (n = 35). After 28 days of follow-up, all patients were followed up at 3, 6, 9, and 12 months to assess the safety and efficacy of the treatment.
The results of the study showed that UC-MSCs still improved the whole lung lesions of severe COVID-19 patients after 3 months of administration. Compared with the placebo group, the UC-MSCs-administered group achieved greater remission of solid lung lesions at each follow-up time point, with the most significant difference at month 9. At month 12, 17.9% (10/56) of patients in the UC-MSCs group had normal CT images, while none in the placebo group were normal. In addition, during the 12-month follow-up period, no adverse events related to UC-MSCs infusion were observed. The incidence of adverse events and tumor markers assessed were similar in the UC-MSCs group and the placebo group.
The results of the study showed that UC-MSCs still improved the whole lung lesions of severe COVID-19 patients after 3 months of administration. Compared with the placebo group, the UC-MSCs-administered group achieved greater remission of solid lung lesions at each follow-up time point, with the most significant difference at month 9. At month 12, 17.9% (10/56) of patients in the UC-MSCs group had normal CT images, while none in the placebo group were normal. In addition, during the 12-month follow-up period, no adverse events related to UC-MSCs infusion were observed. The incidence of adverse events and tumor markers assessed were similar in the UC-MSCs group and the placebo group.
6-MWD is an important parameter reflecting the comprehensive reserve capacity of complex physiology, including the pulmonary and cardiovascular systems and neuromuscular circulation. Compared with the placebo group, patients in the UC-MSCs group had increased 6-MWD values at each follow-up node. This may be due to the improvement of lung injury and the recovery of lung reserve capacity after UC-MSC administration.
Common symptoms such as fatigue, muscle weakness, and difficulty sleeping are still present in patients with COVID-19 6 months after onset. Physiological abnormalities of the lungs can still be observed in some patients 12 months after discharge. Consistent with previous studies, 68.6% of enrolled patients still had at least one symptom at 12-month follow-up. Compared with the placebo group, patients treated with UC-MSCs had less symptoms and better quality of life, with significant improvements in sleep difficulties, daily activities, and NRS scores. The underlying mechanism of the action of MSCs has not been fully elucidated. It is speculated that the secretion of hepatocyte growth factor, vascular endothelial growth factor and keratinocyte growth factor from MSCs promotes the regeneration of alveolar type II epithelial cells and improves lung injury. In addition, MSCs can be attracted to the site of inflammation by the corresponding chemokines, and then exert long-term effects by regulating the functions of various immune cells through direct contact and paracrine effects.
Neutralizing antibodies in the patients gradually decreased over time, and at 12 months, the neutralizing antibodies of the two groups of patients were still positive for IR, and the median inhibition rate was similar (61.6%: 67.6%), which indicated that UC-MSCs treatment The production and maintenance of neutralizing antibodies in patients was not affected. The above results show that the administration of umbilical cord-derived mesenchymal stem cells not only achieved beneficial short-term efficacy, but also played a long-term therapeutic role in the lung lesions of severe COVID-19 patients with good tolerance.
Feasibility of MSC Therapy for Covid-19 is clinically validated
After the outbreak of the novel coronavirus pneumonia (COVID-19), the state urgently launched the "Clinical Research on the Use of Human Stem Cells for the Treatment of 2019-nCoV Infected Pneumonia", "CAStem Cell Drug Treatment for Severe New Coronary Pneumonia" and "Interim Research on the Treatment of New Coronary Pneumonia". "Mesenchymal Stem Cell Therapy Research" and other emergency scientific and technological research projects.
With the release of my country's first "Expert Consensus on Mesenchymal Stem Cell Therapy for Novel Coronavirus Pneumonia", the clinical research on mesenchymal stem cell therapy for novel coronavirus pneumonia in China will be more and more intensive. We also look forward to the early arrival of stem cell drug for new coronary pneumonia and the early end of the epidemic!
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