Treatment with Mesenchymal Stromal Cells Overexpressing Fas-Ligand Ameliorates Acute Graft-versus-Host Disease in Mice.
Andrei Mircea VacaruAna-Maria MaziluMadalina DumitrescuIoana Madalina FenyoAnca Violeta GafencuAna Maria VacaruPublished in: International journal of molecular sciences (2022)
Allogeneic hematopoietic cell transplantation (allo-HCT) has the potential to cure malignant and non-malignant hematological disorders, but because of the serious side effects of this intervention its applications are limited to a restricted number of diseases. Graft-versus-host disease (GvHD) is the most frequent complication and the leading cause of mortality and morbidity following allo-HCT. It results from the attack of the transplanted T cells from the graft against the cells of the recipient. There is no clear treatment for this severe complication. Due to their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed to treat GvHD, but the results did not meet expectations. We have previously showed that the immunomodulatory effect of the MSC was significantly enhanced through adenoviral-mediated overexpression of FasL. In this study, we have tested the properties of FasL-overexpressing MSC in vivo, in a mouse model for acute GvHD. We found that treatment with FasL-overexpressing MSC delayed the onset of the disease and increased survival of the mice.
Keyphrases
- mouse model
- randomized controlled trial
- liver failure
- cell cycle arrest
- allogeneic hematopoietic stem cell transplantation
- stem cell transplantation
- low dose
- type diabetes
- induced apoptosis
- respiratory failure
- oxidative stress
- high dose
- hepatitis b virus
- combination therapy
- cardiovascular events
- signaling pathway
- climate change
- extracorporeal membrane oxygenation
- skeletal muscle
- acute myeloid leukemia
- mechanical ventilation