Additive Therapeutic Effects of Mesenchymal Stem Cells and IL-37 for Systemic Lupus Erythematosus

作者：Jianyong Xu, Jieting Chen, Wenlei Li, Wei Lian, Jieyong Huang, Baoyu Lai, Lingyun Li, Zhong Huang · 发表于：Journal of the American Society of Nephrology · 年份：2019 · DOI：10.1681/asn.2019050545 · 被引用次数：82 · 研究领域：Mesenchymal stem cell research、Bone and Joint Diseases、Psoriasis: Treatment and Pathogenesis

Significance Statement Although mesenchymal stem cells might have potential for treating SLE, their immunoregulatory plasticity renders their therapeutic effects unpredictable. The authors genetically modified mesenchymal stem cells to overexpress IL-37—a protein with immunosuppressive activity—and assessed the modified cells’ effects on immune suppression in vitro , as well as the effects of transplanting such cells into a mouse model of SLE. Mice transplanted with IL-37–overexpressing cells displayed improved survival and reduced signs of SLE compared with controls. Expression of IL-37 by mesenchymal stem cells can maintain higher serum levels of IL-37, and these cells had prolonged survival after transplantation, perhaps through IL-37 suppressing the inflammatory microenvironment. The additive therapeutic effects of this approach might offer a way to enhance the stability and effectiveness of mesenchymal stem cells in treating SLE. Background Although mesenchymal stem cells (MSCs) might offer a promising strategy for treating SLE, their immunoregulatory plasticity makes their therapeutic effects unpredictable. Whether overexpressing IL-37, an IL-1 family member with immunosuppressive activity, might enhance the therapeutic effects of these cells for SLE is unknown. Methods We genetically modified MSCs to overexpress IL-37 and assessed their effects on immune suppression in vitro . We also evaluated the effects of such cells versus effects of various controls after transpla...