间充质干细胞,COVID-19 z-bo 2020-10-07 377

　　In a recent preliminary study conducted in China, 7 COVID-19 patients received intravenous injections of donor mesenchymal stem cells (MSCs)-pluripotent cells, which are believed to have immunomodulatory effects, as a result of this intervention Shows that it is safe and the method has the potential to improve the prognosis of patients. Seven patients have recovered, but scientists have different opinions on the logic behind the method and its actual effects.

　　On April 5 this year, the U.S. Food and Drug Administration (FDA) approved the use of MSC to treat the most severe COVID-19 patients who have been used sympathetically for a long time. Christine Mummery, a developmental biologist and stem cell researcher at Leiden University in the Netherlands, said: "The rationale for this [Chinese] study is not yet clear and its effectiveness is uncertain. People need to stay healthy. . Please stay skeptical." Mamelie expressed interest.

　　Ashok Shetty, a regenerative medicine researcher at the Texas A&M University School of Medicine, disagrees with this view. He sent an email to the "Scientist" magazine by email. The results of a Chinese study showed that: "Intravenous injection of MSC is a safe and effective way to treat patients with COVID-19 pneumonia, including elderly patients with severe pneumonia. But it needs to be tested in a larger patient cohort to verify these benefits," Shetti said. "I am not interested in companies that provide MSCs for treatment. I did not participate in this research. Despite being "competitive," we previously received project funding from CellTex, a company engaged in MSC-based treatments, for research unrelated to Alzheimer's disease. As a disease caused by the new SARS-CoV-2 coronavirus, COVID-19 can show completely different clinical manifestations. Some infected people have no symptoms, while others have mild illnesses, such as flu. In severe pneumonia, some patients will die.

　　cytological release syndrome

　　Most critically ill patients seem to have the pathological phenomenon that is frequently observed --- as observed in sepsis, the immune response is uncontrolled. This pathological phenomenon is called cytokine release syndrome, or more commonly called cytokine storm. Cytokines are small proteins released by immune cells. In the face of foreign invaders, they regulate the attack and destruction of the host's immune system. However, elevated levels of these proteins can cause the immune system to overwork, damage the patient’s own tissues and organs, and are usually fatal.

　　The reason for conducting preliminary research in China is that MSC may help resist the cytokine storm. MSCs are pluripotent cells found in various parts of the human body (including bone marrow, placenta and umbilical cord) and are reported to have immunomodulatory effects. In fact, based on this ability, MSCs isolated from donors are cultured and propagated, and then injected into patients as an experimental method to treat many different diseases. For example, clinical trials are currently underway to study the use of MSCs in the treatment of acute respiratory distress syndrome (ARDS)-fluid accumulation in the lungs causes severe hypoxia. ARDS is a common symptom of cytokine storm and the cause of death for many COVID-19 patients.

　　As Mummery said, the evidence for effective regulation of the immune response is "not strong enough." She said: "The results of many clinical trials show that the clinical results are not important," with the significant changes in the MSC source tissue. The type of cells injected is also very different. The mechanism of action is unknown. When she talked about whether they would work, she said: "Some people believe it, some people don't."

　　As a cytokine storm expert at the University of Alabama at Birmingham, he pointed out that there are other therapeutic cytokines. Storm's drugs are in clinical trials, including tosirizumab, which was recently approved for the treatment of severe COVID-19 cases in China and the United States. He said that for COVID-19 treatment, "I am not the first person to think of MSC" because MSC treatment is more experimental, but "if it works, it will work." Krona is associated with certain pharmaceutical companies that make drugs to treat cytokine storms.

　　In Japan, MSC has been approved for the treatment of another form of cytokine storm, namely implant-to-host disease, and is awaiting US approval. There are also some clinical trials beginning to test the benefits of using MSC to treat COVID-19. Martin Grumet, a stem cell researcher at Rutgers University and the chief scientific officer of CytoStormx, who developed MSC processing technology, said: "There is a lot of indirect evidence that [MSC] should play a role in this field. There is." Grumet did not participate in Chinese studies. But he thinks the data looks promising.

　　The clinical results of using MSC to treat COVID-19 are in  a Chinese study published in the Journal of Aging and Disease, 7 patients with COVID-19-1 severely ill and 4 severely ill, received intravenous MSC injection in two mild patients. In all cases, these patients had recovered by the end of the 14-day observation period, and some of them had been discharged from the hospital. In contrast, 3 patients in the placebo control group died, 1 developed ARDS, and 1 was stable. Daniel O'Toole of the National University of Ireland (who was not involved in the study) found that the oldest patients in the treatment group were the two worst patients (one death and one ARDS). The age I pointed out is about 10 years old. He said: "It is very certain that the relationship between [COVID-19 patient mortality] and age may be greater than any other factor." This may bias the results of these studies. It shows that there is. O'Toole has no conflicts of interest to declare.

　　In addition to these seven patients, another 65-year-old female COVID-19 patient received MSC treatment in the paper submitted to the preprinted website ChinaXiv at the end of February. Her condition has also improved, but Keren said: "Judging from at least many test markers, the patient's condition improved before receiving MSC [treatment]." Therefore, the results are "convincing." Kunlin Jin of the University of North Texas Health Science Center said: "I understand these are just a few examples." However, the results show that "MSC is a very promising treatment for COVID-19. "

　　Paul Knoepfler, a stem cell biologist at the University of California, Davis, writes in the journal "Scientist". I don’t believe it,” he wrote in an email. The diseases are so diverse and the number of people studied is so small that “they cannot get information about the efficacy from a small number of patients.” He added that they didn’t even It really shows that this method is safe. Considering that MSC is believed to suppress immunity, "MSC may also weaken the body's overall immune response to the new coronavirus. "Knoepfler has no conflict of interest to declare.

　　Mummery said: "We are very happy that not all of these patients died suddenly after injecting MSC into these patients." However, I agree with Knoepfler's view that it is too early to judge safety. MSC is generally considered safe and well tolerated by patients, but "I don't know what the safety record is for this particular patient group."

　　Doctor will soon have more data about safety and effectiveness you may get. Lynn told The Scientist that his team has not yet released data on the 24 patients treated with MSC, claiming that their condition has improved. The FDA recently approved this treatment (extreme cases and clinical trials) and recruited COVID-19 patients around the world to participate in existing clinical trials using MSC to treat ARDS. This means that clinical data can be very large. Will be announced soon. Ott said: "Unfortunately, I think there will be a lot of patients soon, because there may be no other patients in the intensive care unit (ICU) except for COVID-19 ARDS patients."