Transplanted MusSCs restored hind limb function in immune-suppressed mice.
Stanford University scientists report that they have demonstrated for the first time that a single adult stem cell can repair tissue damage in a live mammal.
The researchers transplanted the skeletal adult muscle stem cells (MusSCs) into special immune-suppressed mice whose muscle satellite cells had been wiped out in a hind limb by irradiation. The stem cells restored lost function to mice with hind limb muscle tissue damage, according to the team.
The adult stem cells used in the study were isolated from a mixed population of satellite cells from the skeletal muscle of mice. Investigators genetically engineered the transplanted MusSC to express Pax7 and luciferase proteins. As a result, every transplanted cell glowed under ultraviolet light and was easy to trace.
The team used luminescent imaging as well as quantitative and kinetic analyses to track each transplanted stem cell as it rapidly proliferated and engrafted its progeny into the irradiated muscle tissue.
The scientists then injured the regenerated tissue, setting off muscle cell growth and repair, and subsequently showed that the MuSC and descendents rescued the second animal’s lost muscle healing function.
After isolating the luciferase-glowing muscle stem cells from the transplanted animal, the scientists cloned the cells in the lab. Like the original MuSC, the cloned copies were intact and capable of self renewal.
In further experiments, the researchers transplanted between 10 and 500 luciferase-tagged MuSC into the leg muscles of mice. These cells also proliferated and engrafted, forming new myofibers and fusing with injured fibers.
Unlike tumor cells, the transplanted stem cells achieved homeostasis, growing to a stable, constant level and ceasing replication. After demonstrating that the transplanted stem cells proliferated and fully restored the animal’s lost function, the scientists recovered new stem cells from the transplant with full stem cell potency.
This research was reported at the 48th annual meeting of the American Society for Cell Biology (ASCB) on Sunday, December 14 in San Francisco.
