Therapeutic potential of mesenchymal stem cells in multiple organs affected by COVID-19.

Currently, the world has been devastated by an unprecedented pandemic in this century. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), has been causing disorders, dysfunction and morphophysiological alterations in multiple organs as the disease evolves. There is a great scientific community effort to obtain a therapy capable of reaching the multiple affected organs in order to contribute for tissue repair and regeneration. In this regard, mesenchymal stem cells (MSCs) have emerged as potential candidates concerning the promotion of beneficial actions at different stages of COVID-19. MSCs are promising due to the observed therapeutic effects in respiratory preclinical models, as well as in cardiac, vascular, renal and nervous system models. Their immunomodulatory properties and secretion of paracrine mediators, such as cytokines, chemokines, growth factors and extracellular vesicles allow for long range tissue modulation and, particularly, blood-brain barrier crossing. This review focuses on SARS-CoV-2 impact to lungs, kidneys, heart, vasculature and central nervous system while discussing promising MSC's therapeutic mechanisms in each tissue. In addition, MSC's therapeutic effects in high-risk groups for COVID-19, such as obese, diabetic and hypertensive patients are also explored.

Early proliferation of bone marrow mononuclear cells on collagen membrane, bone graft and tooth cementum / Proliferación temprana de células mononucleares de médula óseasobre membrana de colágeno, injerto óseo y cemento dentario

The ultimate goal of periodontal therapy is to repair the damaged periodontal supporting tissues, permitting regeneration of the periodontal ligament. However, the cell response, the supportive matrix and the bioactive molecules use have not yet been well established. Bone marrow mononuclear cells were extracted from rat femurs and tibiae and cultured on a cross-linked collagen membrane, bone graft, or molar tooth to compare cell attachment and early proliferation on these materials. Cell attachment was quantified by light microscopy at 24, 48 and 72h, and cell proliferation was observed under a SEM after 72h. After 24h, the number of cells on bone graft was similar to that of the control and more than twice compared to collagen membrane (q=7.473 p<0.001) and 1.75 times greater than with tooth cementum (q=5.613 p<0.01). However, the number of cells close to bone graft decreased in the second day compared to the control. SEM examination revealed a significant decrease in the number of cells that attached and proliferated on tooth and bone graft when compared with membrane. The results showed that bone marrow mesenchymal cells offer great potential for colonize a collagen membrane.

El objetivo último de la terapia periodontal es reparar el daño tejidos periodontales de soporte, permitiendo la regeneración del ligamento periodontal. Sin embargo, la respuesta de la célula, la matriz de apoyo y las moléculas bioactivas aún no han sido bien establecidas. Células mononucleares de la médula ósea se extrajeron del fémur y fibula de rata, y fueron cultivadas sobre un reticulado de membrana de colágeno, de injerto de hueso o de un diente molar para comparar la adhesión celular y la proliferación temprana sobre estos materiales. La adhesión celular fue cuantificada por microscopía de luz a las 24, 48 y 72h, y la proliferación celular fue observada bajo MEB después de 72h. Después de 24 horas, el número de células sobre el injerto de hueso fue similar a la del control y más del doble en comparación con la membrana de colágeno (q=7,473 p<0,001) y 1,75 veces mayor que con el cemento dental (q=5,613 p<0,01). Sin embargo, el número de células cerca del injerto óseo disminuyó el segundo día en comparación con el control. El examen al MEB reveló una disminución significativa en el número de células que se unen y proliferan sobre los dientes y el injerto óseo en comparación con la membrana. Los resultados mostraron que las células mesenquimales de la médula ósea tienen un gran potencial para colonizar la membrana de colágeno.

Osteopontin expression in coculture of differentiating rat fetal skeletal fibroblasts and myoblasts.

Skeletal fibroblasts in vitro can acquire myofibroblast phenotypes by the development of biochemical and morphological features, mainly the expression of alpha-smooth-muscle actin (alpha-SMA). Myogenic differentiation is a central event in skeletal muscle development, and has commonly been studied in vitro in the context of skeletal muscle development and regeneration. Controlling this process is a complex set of interactions between myoblasts and the extracellular matrix. Osteopontin (OPN) is an acidic, phosphorylated matrix protein that contains an Arg-Gly-Asp (RGD) cell attachment sequence and has been identified as an adhesive and migratory substrate for several cell types. The aim of this study was to investigate osteopontin expression during the differentiation of skeletal fibroblasts into myofibroblasts and during myogenesis in a coculture model. Fibroblasts and myoblasts were obtained from skeletal muscle of 18-d-old Wistar strain rat fetuses by enzymatic dissociation. At 1 and 9 d, cocultures were immunolabeled, and the cells were also separately subjected to Western blotting to analyze OPN expression. Our data using confocal microscopy showed that myoblasts displayed a strong staining for OPN and that this labeling was maintained after myotube differentiation. Conversely, during fibroblast differentiation into myofibroblasts, we observed a significant increase in OPN expression. The results obtained by immunolabeling were confirmed by Western blotting. We suggest that OPN is important mainly during early stages of myogenesis, facilitating myoblast fusion and differentiation, and that the increased expression of OPN in myofibroblasts might be related to its effects as a key cytokine regulating tissue repair and inflammation.