Enrichment of Human ESC-Derived Multipotent Mesenchymal Stem Cells with Immunosuppressive and Anti-Inflammatory Properties Capable to Protect Against Experimental Inflammatory Bowel Disease

• DOI: 10.1002/stem.569
• Publication Date: 2010-11-23T19:14:36Z
• Authors: Laura Sánchez; Iván Gutierrez-Ar...; Gertrudis Ligero; Ruth Rubio; Martín Muñoz-López; José L. García-Pérez; Verónica Ramos; Pedro. J. Real; Clara Bueno; René Rodríguez; Mario Delgado; Pablo Menendez
• Keywords: CD90; Multipotent Stem Cell; Regenerative Medicine

Human ESCs provide access to the earliest stages of human development and may serve as an unlimited source functional cells for future cell therapies. The optimization methods directing differentiation embryonic stem (hESCs) into tissue-specific precursors becomes crucial. We report efficient enrichment mesenchymal (MSCs) from hESCs through specific inhibition SMAD-2/3 signaling. ESC-derived MSCs (hESC-MSCs) emerged a population fibroblastoid expressing MSC phenotype: CD73+ CD90+ CD105+ CD44+ CD166+ CD45- CD34- CD14- CD19- leucocyte antigen-DR (HLA-DR)-. After 28 days inhibition, hESC cultures were enriched (>42%) in multipotent MSCs. CD73+CD90+ hESC-MSCs fluorescence activated sorting (FACS)-isolated long-term established maintained many passages displaying faster growth than somatic tissue-derived while maintaining morphology phenotype. They displayed osteogenic, adipogenic, chondrocytic potential exhibited potent immunosuppressive anti-inflammatory properties vitro vivo, where capable protecting against experimental model inflammatory bowel disease. Interestingly, signaling was not reproducible with distinct induced pluripotent lines. Our findings mechanistic insights clinical applications.