Gene Regulation and Molecular Therapies Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu", 050568 Bucharest, Romania.
Int J Mol Sci. 2022 Jan 4;23(1):534. doi: 10.3390/ijms23010534.
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.
异基因造血细胞移植（allo-HCT）有治愈恶性和非恶性血液病的潜力，但由于这种干预的严重副作用，其应用仅限于少数几种疾病。移植物抗宿主病（GvHD）是 allo-HCT 后最常见的并发症和主要死亡原因和发病率。它是由移植物中的移植 T 细胞攻击受体细胞引起的。对于这种严重的并发症，目前还没有明确的治疗方法。由于间充质基质细胞（MSC）具有免疫调节特性，因此有人提出用 MSC 治疗 GvHD，但结果并不理想。我们之前曾表明，通过腺病毒介导的 FasL 过表达可显著增强 MSC 的免疫调节作用。在这项研究中，我们在急性 GvHD 的小鼠模型中测试了 FasL 过表达 MSC 的体内特性。我们发现，用 FasL 过表达 MSC 治疗可延迟疾病的发作并提高小鼠的存活率。
