Muscle satellite cells are a rare regenerative population in adult skeletal muscle and have potential to repair damaged muscle tissue. In this episode, Simone Spuler and colleagues demonstrate that satellite cells can be successfully expanded from human adult muscle biopsies in culture and transplantation of satellite cell-containing human muscle fiber fragments into irradiated mice restores damaged muscle tissue. Isolated muscle fibers could be stored in the cold for a period of time and still retain the ability to engraft and regenerate muscle. Moreover, Spuler and colleague determined that adult-derived satellite cells could be genetically manipulated with Sleeping Beauty transposon–mediated gene transfer. Together, this study suggests that adult human muscle satellite cells have potential as a gene therapy tool for treating muscular dystrophies.
Napoleone Ferrara, of the University of California, San Diego, is best known for isolating and cloning vascular endothelial growth factor (VEGF). He then built the humanized monoclonal antibody against VEGF that led to the blockbuster drugs Avastin (for treating cancer) and Lucentis (for treating wet age-related macular degeneration).
Age-related declines in immune function result in enhanced susceptibility to infection and decreased vaccine efficacy. While aged immune cells exhibit signs of cellular senescence, such as a reduced proliferative capacity, many maintain effector function. In this episode, Sian Henson discusses the characterization of a subset of human effector memory CD8+ T cells that reexpress the naïve T cell marker CD45RA (EMRA cells). Despite their senescent-like state, EMRA cells exhibited potent cytotoxic activity, the energy for which was generated by anaerobic glycolysis. Inhibition of p38 MAPK signaling in EMSA cells reversed senescent phenotypes and increased autophagy. These results indicate that some aspects of CD8+ T cell senescence may be reversible.
β cell dysfunction is a hallmark of type 2 diabetes (T2D) and is associated with extracellular accumulation of amyloid plaques comprised of islet amyloid polypeptide (IAPP). Human IAPP is potentially toxic and has been shown to accumulate within β cells of T2D patients and in transgenic rodent models. In this episode, Safia Costes and colleagues examine the role of autophagy in the degradation of human IAPP in murine models. Human IAPP aggregated within p62-positive inclusions in transgenic animals, with no apparent loss of β cell function or mass; however, human IAPP-expressing mice with a β cell-specific autophagy defect developed overt diabetes due β cell death. These results indicate that autophagy is protective against IAPP-induced toxicity in β cells and suggest the autophagy pathway as a potential theraputic target for treatment and/or prevention of T2D.
In virto fertilization (IVF) has helped millions of couples have children. While considered relatively safe, there are risks associated with this procedure. Among the more serious complications is the development of ovarian hyperstimulation syndrome (OHSS), which in extreme cases can be fatal. OHSS results from excessive stimulation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG), which is commonly used as part of the IVF cycle to promote egg maturation. In this episode, Waljit Dhillo discusses the results from a small clinical trial that evaluated use of the fertility hormone kisspeptin-54 for egg maturation in IVF. Dhillo and colleagues report that kisspeptin-54 treatment resulted in mature eggs that were successfully fertilized and transferred, with pregnancy in 23% of patients.