In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3(-/-), Nes-Socs3(-/-)). Reactive astrocytes in Nes-Stat3(-/-) mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3(-/-) mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT + serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPSderived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that preevaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.neural stem/progenitor cell | cell transplantation | regenerative medicine | remyelination | axonal regrowth

In pancreatic adenocarcinoma, the presence of CD4+ TILs together with CD8+ TILs serves as a good indicator of the patient's outcome after surgical treatment.