Incorporation and differentiation of hippocampus-derived neural stem cellstransplanted in injured adult rat retina

PURPOSE. In a previous study it has been shown that adult rat hippocampus-d erived neural stem cells can be successfully transplanted into neonatal ret inas, where they differentiate into neurons and glia, but they cannot be tr ansplanted into adult retinas. In the current study, the effect of mechanic al injury to the adult retina on the survival and differentiation of the gr afted hippocampal stem cells was determined. METHODS. Mechanical injury was induced in the adult rat retina by a hooked needle. A cell suspension (containing 90,000 neural stem cells) was slowly injected into the vitreous space. The specimens were processed for immunohi stochemical studies at 1, 2, and 4 weeks after the transplantation. RESULTS. In the best case, incorporation of grafted stem cells was seen in 50%:, of the injured retinas. Most of these cells located from the ganglion cell layer through the inner nuclear layer close to the injury site. Immun ohistochemically, at 1 week, more than half of the grafted cells expressed nestin. At 4 weeks, some grafted cells showed immunoreactivity for microtub ule-associated protein (MAP) 2ab, MAP5, and glial fibrillary acidic protein (GFAP), suggesting progress in differentiation into cells of neuronal and astroglial lineages. However, they showed no immunoreactivity for HPC-1, ca lbindin, and rhodopsin, which suggests that they did not differentiate into mature retinal neurons. Immunoelectron microscopy revealed the formation o f synapse-like structures between graft and host cells. CONCLUSIONS. By the manipulation of mechanical injury, the incorporation an d subsequent differentiation of the grafted stem cells into neuronal and gl ial lineage, including the formation of synapse-like structures, can be ach ieved, even in the adult rat retina.