Fig. 6

Pharmacological targeting of Cdc42 activity by ML141 (ML) induces rifampicin responsiveness and restores cell function. hADSCs derived from young and aged subjects were differentiated and treated with or without ML141 as indicated in Fig. 4. a–c Secreted albumin, urea production, and low-density lipoprotein (LDL) uptake: supernatants of cultured cells and the lysates were collected at D0/D14/D28 of the differentiation for the quantification of albumin, urea, and LDL uptake as indicated in the Methods. Results are expressed per ng/ml (for the production of albumin and urea) and RFU (fluorescent LDL uptake) and are presented as fold variation relative to young at day D0, and are the mean ± SEM of several measures (5, 6 and 10, respectively). d Cytochrome P450 (CYP3A4) activity at day 28 of the Hep-Dif after induction with rifampicin (20 μM, 24 h). The results are expressed as fold variation relative to basal (without rifampicin), and are the mean ± SEM of three independent experiments performed in duplicate. e hepatocyte-like cells derived from aged ADSCs treated with ML141 exhibit hepatic-specific function of glycogen storage. Cells were evaluated for glycogen storage capacity (pink color) using periodic acid-Schiff (PAS) staining as described in the Methods. Cells were examined microscopically and phase-contrast images were captured. Cultures of HepG2 cells were assessed as positive controls. ^§*P < 0.05, ^§§**P < 0.01; ^§rifampicin versus controls or aged versus young and *aged treated with ML141 versus untreated