Research Assistant Instituto Gorgas de ciencia de la salud de Panamá Panama, Panama, Panama
Abstract: Five years have passed since the COVID-19 pandemic, caused by the SARS-CoV-2 virus, which has left latent risks in patients with inflammatory diseases such as type 1 and type 2 diabetes. Researchers have sought alternatives to mitigate the hyperinflammatory effects of SARS-CoV-2. One promising option is mesenchymal stem cells (MSCs), obtained from various human tissues and recognized for their potential in regenerative medicine due to their high immunomodulatory capacity through the production of pro-/anti-inflammatory cytokines. Recent studies indicate that preactivation of MSCs with cytokines, particularly IFN-γ, enhances their immunomodulatory capacity by reducing the production of proinflammatory cytokines in macrophages, T cells, and NK cells. However, there are currently no standardized methodologies to attenuate the hyperinflammation caused by SARS-CoV-2. In our study, we evaluated the immunomodulatory effect of placenta-derived mesenchymal stem cells (PDMSCs) preactivated with LPS/IFN-γ on peripheral blood mononuclear cells (PBMCs) infected with SARS-CoV-2. We observed increased expression of proinflammatory genes such as IL6 (three-fold increase), COX2 (three-fold increase, two-fold decrease), and IDO (two-fold increase, two-fold decrease) in preactivated PDMSCs, especially when cocultured with SARS-CoV-2-infected PBMCs. In addition, immune markers such as CD36 showed a three-fold decrease and CD25 a two-fold increase in infected PBMCs in contact with stimulated PDMSCs. Preactivated PDMSCs also attenuated the production of intracellular cytokines such as IL6, IL4, IL12, and IL17 in PBMCs (two-fold decrease) in patients exposed to SARS-CoV-2. These results allow us to conclude that the presence of SARS-CoV-2 induces inmune activation by increasing cytokine production by PDMSCs, which in turn exerts an immunomodulatory effect reflected in phenotyping markers and intracellular cytokines in PBMCs. This remarkable attenuation highlights the potential of preactivated PDMSCs for patients with inflammatory pathologies affected by lethal viruses like SARS-CoV-2. These findings contribute to the development of regenerative medicine through immunomodulation treatments, offering new avenues for immune regulation and improving quality of life in the future.
Funding Source: The funding resources are: SENACYT, APANAC and Gorgas Memorial Institute.
