The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial.

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-ß, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

The synergistic effect of ω3 and Vit D3 on glycemia and TNF-α in islet transplantation.

The current treatment of type 1 diabetes consists of insulin administration. Transplantation of islets of Langerhans is considered very favorable because the full effect of insulin treatment cannot be obtained in severe cases. Although agents such as omega-3 (ω3) and vitamin D3 (Vit D3) are known to contribute to the success of islet allo-transplantation (ITX), in this study we aimed to experimentally determine their effects on glycemia and TNF-α production. Wistar albino rats, which were used as recipients, were given ω3, Vit D3, and islets by gavage, and intraperitoneal- and intraportal injections, respectively. Daclizumab (DAC) was used for immunosuppression. Glycemia levels decreased in rats treated with ω3 and vit D3. TNF-α increased in all groups due to application of STZ. After ITX (day +1), the weakest increase was observed in the ω3 + Vit D3 group. In the ITX+DAC group, compared with that of ITX only, DAC was shown to decrease levels of TNF- α following ITX, only in control group, however, similar levels of TNF-α were observed in other groups. The values in the treated groups were already lower than those of the controls in the ITX group and also remained almost equal in the ITX+DAC group. We suggest that the use of ω3 and Vit D3 together will improve the pro-inflammatory aspect encountered during and after ITXs, and contribute to the reduction of the dose of immunosuppressants in these procedures.