Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.

[Glaucoma model for stem cell transplantation research in New Zealand white rabbits].

Glaucoma is a typical irreversible blind neurodegenerative disease for which there is no effective treatment for halting visual deterioration. The recent development of neural stem cells studies sheds light on a potential resolution for this disease. As a result, an appropriate glaucoma modeling method for stem cell transplantation study is needed. In the present study, Dexamethasone was injected unilaterally into the conjunctiva of New Zealand rabbit at the dose of 2.5 mg (5 mg/mL), three times a week. After eight weeks, the eye ground photography showed that the optic nerve head of the treated eye was expanded, and the blood vessel was geniculate compared to the control eye, while the ocular media remained transparent. The hematoxylin-eosin (HE) stain of the retinal nerve fiber layer (RNFL) sections showed optic neuron death in the treated eye. The Heidelberg Retina Tomography (HRT) results showed optic disk morphological changes consistent with the pathophysiology of glaucoma in the treated eye, including a decrease in the rim area (1.10±0.88) mm(2) and mean RNFL thickness (0.44±0.31) mm, and an increase in the cup/disk ratio 0.17±0.13. Then neural stem cells were injected into the vitreous body of the treated eye. After five months, surviving transplanted cells were observed. These results suggest a simple and reproducible chronic glaucoma model, which is appropriate for neural stem cell transplant research, has been successfully developed.

[A traumatic brain injury model for distinguishing between transplanted neural cells and host cells in vivo].

To perform electrophysiological recording and other investigations on transplanted neural cells in vivo, we used mechanical damage to establish a special traumatic brain injury model that could distinguish transplanted cells from host cells. The morphology of the trauma-induced holes in the cortex of the rat brain was regular. The model was stable and repeatable. Neural stem cells were transplanted into the trauma-induced hole, and were able to survive for a long time. Most of the transplanted cells differentiated into neurons, and only a small amount turned into glia cells. There was a clear boundary between the host cells and the transplanted cells. Single cell electrophysiological recording on transplanted neural cells were detected in vivo. This study established a stable and repeatable traumatic brain injury model, which could be used to conduct in vivo electrophysiological recording research on transplanted neural cells.