Neural Stem Cell Dissemination after Grafting to CNS Injury Sites

Steward and colleagues report that implants of E14 rat spinal-cord-derived multipotent neural progenitor cells are associated with ectopic deposits of cells, occasionally at long distances from a T3 spinal cord lesion and grafting site. Of 20 grafted rats, half showed ectopic cell deposits. One rat had a deposit of cells in the 4 ventricle, from which relatively few axons extended into the tegmentum. Half of animals had cells within six spinal segments of the lesion site, and of these, three had deposits more distantly. There is a long and well-established precedent for the finding that neural stem cells and other nervous system cells can spread over extended distances through the adult nervous system (Fricker et al., 1999, Li et al., 2003, Han et al., 2004, Guzman et al., 2007, Pearse et al., 2007, Goldman et al., 2012). Previous reports have also specifically documented spread of implanted cells through the central canal and subpial region (Li et al., 2003, Pearse et al., 2007). Re-examination of specimens from our original report (Lu et al., 2012) confirms that ectopic cell deposits were found in three of six animals with complete transections. A few points should be noted in interpreting findings specific to our experiment and the letter of Steward et al. (2014). First, in our experiment and that of Steward et al., injections into the lesion cavity in rats were made using a PicoSpritzer (General Valve), which generates pulses of relatively high pressure (in excess of 1,000 mm Hg). For comparison, human blood pressure typically reaches a peak systolic pressure of 120 mm Hg. This high pressure would tend to force cells from the lesion site and cause remote cell dissemination (Lu et al., 2006, Pearse et al., 2007). Lower pressure injections might be associated with lower risk. Indeed, in nonhuman primates (rhesus monkeys)