MANF Produced by MRL Mouse-Derived Mesenchymal Stem Cells Is Pro-regenerative and Protects From Osteoarthritis

The super healer Murphy Roths Large (MRL) mouse represents the “holy grail” of mammalian regenerative model to decipher key mechanisms that underlies regeneration in mammals. At a time when mesenchymal stem cell (MSC)-based therapy most promising approach treat degenerative diseases such as osteoarthritis (OA), identification factors responsible for potential MSC derived from MRL would be major step forward medicine. In present study, we assessed and compared (MRL MSC) C57BL/6 (BL6 mice. First, compare phenotype differentiation BL6 did not observe any difference. Then, evaluated proliferation migration cells found while proliferate at slower rate than MSC, they migrate significantly higher rate. This is mediated, part, by MSC-secreted products since conditioned medium contains complex released increased MSC. A comparative analysis secretome quantitative shotgun proteomics Western blotting revealed produce release levels mesencephalic astrocyte-derived neurotrophic factor (MANF) BL6, BALB/c, DBA1 MANF knockdown using specific small interfering RNA (siRNA) reduced both scratch wound assay their ear punch Finally, injection silenced protect mice OA development. conclusion, our results evidence enhanced protection might be, attributed an effective reservoir MANF.