Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis

Abstract Background To investigate the in vitro and vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that do not require prior cell priming to acquire a robust immunomodulatory phenotype order efficiently reverse synovitis IFP fibrosis, secondarily delay articular cartilage damage vivo. Methods Human immunophenotype, tripotentiality, transcriptional profiles were assessed settings. Multiplex secretomes spheroids [Crude (non-immunoselected), CD146 + or − immunoselected cells] compared with 2D cultures without inflammatory/fibrotic priming. Functionally, for their immunopotency on human PBMC proliferation effect stimulated synoviocytes inflammation fibrotic cues. The anti-inflammatory anti-fibrotic spheroid properties further evaluated rat model acute synovitis/fat pad fibrosis. Results Spheroids enhanced phenotypic, transcriptional, secretory cultures. Further, showed profiles; however, these attributes reflected superior suppress activated PBMC. This suggests culturing settings are sufficient induce an both Crude CD146-immunoselected IFP-MSC. modulated molecular response previously exposed inflammatory Therapeutically, retained substance P degradation potential vivo, while effectively inducing resolution inflammation/fibrosis synovium fat pad. Furthermore, presence resulted arrest progressive Conclusions confer reproducible circumventing requirement non-compliant selection before administration thereby streamlining products manufacturing protocols.