Awakening adult neural stem cells: NOX signalling as a positive regulator of the quiescence-to-proliferation transition in the Xenopus retina.

A growing wealth of data suggest that reactive oxygen species (ROS) signalling might be crucial in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ROS production and scavenging, and how ROS in turn contribute to stemness, remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared with progenitors and retinal neurons, and express a set of specific redox genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase-dependent ROS production increases the proportion of quiescent RSCs. Surprisingly, this is accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NADPH oxidase signalling to limit quiescence and fine-tune their proliferation rate.

Beneficial Effects of Hyaluronan-Based Hydrogel Implantation after Cortical Traumatic Injury.

Traumatic brain injury (TBI) causes cell death mainly in the cerebral cortex. We have previously reported that transplantation of embryonic cortical neurons immediately after cortical injury allows the anatomical reconstruction of injured pathways and that a delay between cortical injury and cell transplantation can partially improve transplantation efficiency. Biomaterials supporting repair processes in combination with cell transplantation are in development. Hyaluronic acid (HA) hydrogel has attracted increasing interest in the field of tissue engineering due to its attractive biological properties. However, before combining the cell with the HA hydrogel for transplantation, it is important to know the effects of the implanted hydrogel alone. Here, we investigated the therapeutic effect of HA on host tissue after a cortical trauma. For this, we implanted HA hydrogel into the lesioned motor cortex of adult mice immediately or one week after a lesion. Our results show the vascularization of the implanted hydrogel. At one month after HA implantation, we observed a reduction in the glial scar around the lesion and the presence of the newly generated oligodendrocytes, immature and mature neurons within the hydrogel. Implanted hydrogel provides favorable environments for the survival and maturation of the newly generated neurons. Collectively, these results suggest a beneficial effect of biomaterial after a cortical traumatic injury.

Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson's Disease.

Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson's disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson's disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.