Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

Protocol dependence of the jamming transition.

We propose a theoretical framework for predicting the protocol dependence of the jamming transition for frictionless spherical particles that interact via repulsive contact forces. We study isostatic jammed disk packings obtained via two protocols: isotropic compression and simple shear. We show that for frictionless systems, all jammed packings can be obtained via either protocol. However, the probability to obtain a particular jammed packing depends on the packing-generation protocol. We predict the average shear strain required to jam initially unjammed isotropically compressed packings from the density of jammed packings, shape of their basins of attraction, and path traversed in configuration space. We compare our predictions to simulations of shear strain-induced jamming and find quantitative agreement. We also show that the packing fraction range, over which shear strain-induced jamming occurs, tends to zero in the large system limit for frictionless packings with overdamped dynamics.