The Aggregates of Mesenchymal stem cell with Cadherin/IGF1 Functionalized PLGA composite Microparticles Improve Systemic Lupus Erythematosus Treatment in MRL/lpr mice
Mesenchymal stem cell (MSC) therapy is a promising candidate for systemic lupus erythematosus (SLE), while more researches are needed to further improve therapeutic efficacy. In this study, engineered MSC aggregates are composited with MSC and cadherin/IGF1 functionalized PLGA composite microparticles, and are able to stimulate the microenvironment in vivo and enhance MSC functions of immunoregulation and cytokine secretion. Comprehensive characterization of these PLGA composite microparticles coated with E-cadherin/N-cadherin, enhancing MSC viability and cytokine secretion, followed by transcriptomic analysis to evaluate their potential advantages. We detected engineered MSC aggregates further ameliorated skin and lupus nephritis, compared with MSCs in MRL/lpr mice. In addition, engineered MSC aggregates enhanced Treg differentiation in vitro and in the spleen and lumph node of MRL/lpr mice. These findings suggested that engineered MSC aggregates represented a promising bioengineered approach for treating SLE, broadening the clinical applications of MSC-based therapies. Overall design: To further understand the functional advantage of the engineered MSC aggregates  over the normal MSC, we conducted RNA-seq analysis to uncover potential enhancements in therapeutic functions