Human 3D Skeletal Microphysiological Systems For Metabolic And Drug Toxicity StudiesWednesday, 8 July 2015 at 18:00 Add to Calendar ▼SELECTBIOenquiries@selectbiosciences.com Skeletal muscle has a key role in mobility and energy metabolism and diabetes. Skeletal muscle is a major site of drug toxicity, causing weakness and muscle loss. With an aging population sarcopenia is becoming more significant and alterations in muscle glucose metabolism lead to the onset of type 2 diabetes. To provide an in vitro functional screen, we developed three-dimensional (3D) human muscle bundles. The muscle cells formed striated multinucleated fibers and the engineered muscle bundles exhibit contraction in response to electrical stimulation and produce tetanus at frequencies above 20 Hz. Contractile force increased with culture time over a five-week period. Further evidence of functional maturity include expression of mature muscle proteins and normal calcium handling. Contractile behavior and myosin heavy chain expression were enhanced by addition of antimiRs to microRNAs 133a and 696. Engineered human muscle bundles exhibited toxicity to cerivastatin at nanomolar does doses whereas toxicity to lovastatin was not observed until doses were in the micromolar range, above typical therapeutic concentrations. Insulin-mediated glucose uptake was 1.5-2 times higher than glucose uptake in the absence of glucose. |