The field of biotechnology is churns with inventive technology demonstrations; this is an era of creativity, unleashed by a rapid advance in knowledge and capabilities. Here, researchers are presented with the challenge of achieving sustained beneficial activation of transplanted stem cells, where culturing the cells with activating signal molecules prior to transplantation produces only a transient effect. They solve the problem by tethering the signal molecules to the stem cell surfaces; the transplanted cells will continue to be stimulated by this signal for as long as they survive. Like all of the best ideas, it is entirely obvious, but only in hindsight.

Muscle ischemia, or damage to muscle from limited oxygen or blood supply, can result from multiple causes, such as injury to a limb or peripheral artery disease. Stem cells derived from a patient’s own fat tissue are known to produce factors that prompt new blood vessels to grow into the damaged muscle, restoring oxygen and nutrients, and to modulate inflammation in the damaged tissues. However, in vivo experiments have shown limited benefits, as the stem cells’ activity seems to decline after injection into the muscle.

A molecule naturally produced in the body called tumor necrosis factor alpha can spur the stem cells to secrete more of the desired factors. Other studies have tried incubating the cells with TNF-alpha before injection, but the effects fade quickly. Researchers decided to try tethering the TNF-alpha directly to the stem cells, creating nanostimulators – nanoparticles laced with TNF-alpha. The nanoparticles bind to a receptor on the surface of the stem cells, providing localized, targeted, and extended delivery of TNF-alpha.

The researchers tested their approach on mice with surgically induced ischemia in one of their hind legs. They isolated the stem cells from fat tissue, mixed them with the nanostimulators and injected them locally to the mice’s affected legs. The researchers saw increased blood flow and oxygen levels in the ischemic legs. They also witnessed improvements in mobility – the treated mice could walk longer distances and their legs were stronger.