Fig. 5: Adaptation and validation of the DART system to treat type1 diabetic mice.
From: An electrogenetic interface to program mammalian gene expression by direct current
a, Scheme showing how encapsulated DART-engineered cells implanted in the back of mice are stimulated. b, Picture showing the customized acupuncture needles connected to the alkaline batteries. c, Fasting glycemia was recorded before implantation (day 0) and for four consecutive weeks after implantation in three groups of T1D mice with DCINS cell implants, namely non-stimulated mice, mice stimulated for 10 s at the implantation site (stimulated) and mice with cell implants stimulated for 10 s with electrodes placed on their back 3 cm away from the implant site (distantly stimulated). Wild-type mice and T1D mice without implants were also used as controls. d, Intraperitoneal GTT was performed on mice 3 d after implantation of microencapsulated cells and after fasting for 8 h. e, Reversibility of DART-mediated glycemic control. Microencapsulated cells were percutaneously electrostimulated at the implantation site while reversing the ON-OFF/OFF-ON stimulation every third day, using 4.5 V DC for 10 s as ON. f, Blood insulin levels of non-stimulated and electrostimulated animals were profiled 1, 2, 3 and 4 weeks after implantation. Stimulated and distantly stimulated (3 cm away from the implant site) groups were treated with 4.5 V DC for 10 s per day (c,f). g, Blood glucose excursions on day 4 after implantation. Blood samples were collected at several time points for analysis of glucose in wild-type mice and T1D mice non-stimulated and stimulated with DC 4.5 V for 10 s. Time zero corresponded to midnight and electrostimulation was performed at 6:00. All data are mean ± s.d.; n = 5; the values were normalized to the wild-type group. The experiment was performed once in g. P values indicates the significance of differences in the mean values; stimulated group versus non-stimulated group (blue) or wild-type group (black) (c,d); stimulated group versus non-stimulated group (g); two groups versus each other (e); and stimulated group versus the indicated group (f).
