The pandemic of 2019 novel coronavirus has prompted researchers around the world to closely study how coronaviruses operate, in order to find ways to counter potential lasting damage from the infection. While doctors around the world are searching for effective antiviral protocols against SARS-CoV-2, several groups of Chinese researchers decided to try a different path.
They’ve noted that deaths of patients are usually caused not by the virus itself but due to inflammation, that is caused by the infection.
Two groups of Chinese medical researchers have attempted to manage coronavirus infection with mesenchymal stem cells. According to their reports, their procedure allowed to decrease levels of inflammation even in critical patients. However, the extent to which stem cells take part in the repair of damaged tissue is currently unclear.
SARS-CoV-2 attaches itself to cells with ACE2 (an enzyme which takes part in the regulation of blood pressure) on their surfaces. Alveolocytes (cells that comprise the inside lung tissue) have a lot of ACE2. Therefore, virus attacks them first, while they secrete anti-inflammatory proteins. Then, the immune system cells (which lack ACE2 protein) join the fight, which, in turn, leads to inflammation in the lungs. In severe cases, it could lead to cytokine storm (an excessive release of anti-inflammatory proteins), which then leads to disruption in pulmonary gas exchange and heart failure.
Therefore, any successful therapy must include immunosuppression. Usually, this role is reserved for glucocorticoids (hormones, produced by adrenal glands) but this approach isn’t always beneficial, sometimes significantly slowing down the removal of the virus from the system. That’s why several groups of doctors decided to use a different type of immunosuppressor – mesenchymal stem cells. They’re known for their ability to release a wide spectrum of anti-inflammatory proteins to protect themselves from immune system cells. In some countries, they’re already being used to decrease inflammation, for instance, during bone marrow transplants or for bowel disorders.
The first group of doctors led by Min Hu of the Peking University decided to use mesenchymal stem cells extracted from an umbilical cord. Their patient was a 65-year-old Chinese woman, that was treated for coronavirus with a standard protocol for about a week. During that time, red cell count kept dropping, while the white cell count kept climbing up. Despite all efforts undertaken by doctors, she remained in serious condition. The patient exhibited signs of respiratory failure, liver damage, anaemia, as well as hypertension, type II diabetes and she also had gastric bleeds.
The patient was injected with 3 injections of umbilical cord-derived mesenchymal stem cells, 1 injection every 3 days. Within 12 days her condition has improved considerably, as her vitals, including white blood count, returned to normal. CT also showed no inflammation spots in the lungs and the patient was discharged from an intensive care unit.
The second group led by Robert Chunhua Zhao from Shanghai University performed a more detailed study. Their sample size was 7 patients, who were responding poorly to the usual antiviral therapy. One of them was in critical condition when the study began, 4 in serious condition, with two others having mild symptoms. All of them received a single injection of mesenchymal stem cells, sourced from the university’s biobank and within the next two weeks, doctors were monitoring their vitals.
Before the injection, all the patients had elevated body temperature and had troubles with breathing. Within 2 to 4 days after the injection, these symptoms disappeared with no indication of rejection, hypersensitivity or any other side effects were noticed by the researchers. Three of those patients were soon discharged (after confirmation that they had no traces of viral RNA) and even the critical condition patient slowly improved to “serious” and then had no symptoms whatsoever. As a control group, three of the patients in the serious condition received placebo. At the end of the observation, one of the patients died, one was suffering from respiratory failure, while the third was stable.
Researchers say that the therapy was successful because of its’ anti-inflammatory effect. They have noticed a quadruple increase in interleukin-10 concentration (it’s an anti-inflammatory protein) after the injection, while tumour necrosis factor (a protein that promotes inflammation) decreased by half.
Also, scientists were able to sequence the RNA from mesenchymal stem cells and they’ve found out that not only they suppress inflammation but also express a range of proteins that stimulate mitosis. Researchers think that mesenchymal stem cells promote healing of damaged areas. Besides, the number of genes that were working in them was similar to genes in alveolocytes. This is a might be a proof of stem cells differentiating into alveolocytes, however, no direct evidence of this is currently available.
The results that Chinese scientists received means that mesenchymal stem cells can help with infections resistant to conventional therapy. Although there is no concrete evidence of their participation in lung tissue regeneration, they change the ratio of anti-inflammatory proteins to inflammation stimulants in the bloodstream, thus lowering the risk of a potential cytokine storm.