Mild Hypoxia Enhances Proliferation and Multipotency of Human Neural Stem Cells

Neural stem cells (NSCs) represent an optimal tool for studies and therapy of neurodegenerative diseases. We recently established a v-myc immortalized human NSC (IhNSC) line, which retains stem properties comparable to parental cells. Oxygen concentration is one of the most crucial environmental conditions for cell proliferation and differentiation both in vitro and in vivo. In the central nervous system, physiological concentrations of oxygen range from 0.55 to 8% oxygen. In particular, in the in the subventricular zone niche area, it's estimated to be 2.5 to 3%.We investigated in vitro the effects of 1, 2.5, 5, and 20% oxygen concentrations on IhNSCs both during proliferation and differentiation. The highest proliferation rate, evaluated through neurosphere formation assay, was obtained at 2.5 and 5% oxygen, while 1% oxygen was most noxious for cell survival. The differentiation assays showed that the percentages of β-tubIII+ or MAP2+ neuronal cells and of GalC+ oligodendrocytes were significantly higher at 2.5% compared with 1, 5, or 20% oxygen at 17 days in vitro. Mild hypoxia (2.5 to 5% oxygen) promoted differentiation into neuro-oligodendroglial progenitors as revealed by the higher percentage of MAP2+/Ki67+ and GalC+/Ki67+ residual proliferating progenitors, and enhanced the yield of GABAergic and slightly of glutamatergic neurons compared to 1% and 20% oxygen where a significant percentage of GFAP+/nestin+ cells were still present at 17 days of differentiation.These findings raise the possibility that reduced oxygen levels occurring in neuronal disorders like cerebral ischemia transiently lead to NSC remaining in a state of quiescence. Conversely, mild hypoxia favors NSC proliferation and neuronal and oligodendroglial differentiation, thus providing an important advance and a useful tool for NSC-mediated therapy of ischemic stroke and neurodegenerative diseases like Parkinson's disease, multiple sclerosis, and Alzheimer's disease

Long-Term Survival of Human Neural Stem Cells in the Ischemic Rat Brain upon Transient Immunosuppression

Understanding the physiology of human neural stem cells (hNSCs) in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs) from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps) upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells) and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably, transplanted IhNSC-P can significantly dampen the inflammatory response in the lesioned host brain. This work further supports hNSCs as a reliable and safe source of cells for transplantation therapy in neurodegenerative disorders

Vpliv marikulture na okolje

The Italian Registry of Thrombosis in Children (RITI) was established by a multidisciplinary team with the aims of improving knowledge about neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols

Screening for Fabry disease in patients with ischaemic stroke at young age: the Italian Project on Stroke in Young Adults

reserved85nomixedPoli, L.; Zedde, Marialuisa; Zini, Andrea; Del Sette, Massimo; Lodigiani, Corrado; Spalloni, Alessandra; Di Lisi, Filomena; Toriello, Antonella; Piras, Valeria; Stilo, Cesare; Tomelleri, Giampaolo; Tancredi, Lucia; Paciaroni, Maurizio; Silvestrelli, Giorgio; Adami, Alessandro; Costa, P.; Morotti, A.; De Giuli, V.; Caria, F.; Gamba, Massimo; Malferrari, Giovanni; Simone, Anna Maria; Musolino, Rossella; Giorli, Elisa; Banfi, Elena; Marcheselli, Simona; Rasura, Maurizia; Pugliese, Nicola; Melis, Maurizio; Bovi, Paolo; Padovani, A.; Burlina, A.; Pezzini, A; Del Zotto, Elisabetta; Giossi, Alessia; Sessa, Maria; Gilberti, Nicola; Magoni, Mauro; Ferrazzi, Paola; Librè, Luca; Rota, Lidia Luciana; Patella, Rosalba; Calabrò, Rocco Salvatore; Bramanti, Placido; La Spina, Paolo; Finocchi, Cinzia; Balestrino, Maurizio; Bruno, Chiara; Massucco, Davide; Gandolfo, Carlo; Traverso, Elisabetta; Delodovici, Maria Luisa; Verrengia, Elena Pinuccia; Carimati, Federico; Bono, Giorgio; Dell'Acqua, Maria Luisa; Bigliardi, Guido; Vandelli, Laura; Nichelli, Paolo Frigio; Carletti, Monica; Cerrato, Paolo; Iacoviello, Licia; Di Castelnuovo, Augusto; de Gaetano, Giovanni; Grassi, Mario; Locatelli, Giampiero; Caso, Valeria; D'Amore, Cataldo; Agnelli, Giancarlo; Checcarelli, Nicoletta; Guidotti, Mario; Arnaboldi, Marco; Giacalone, Giacomo; Zanoli, Elisa; Cavallini, Anna; Persico, Alessandra; Micieli, Giuseppe; Chiti, Alberto; Orlandi, Giovanni; Marchi, Piernicola; Lanari, Alessia; Ciccone, Alfonso; Cucurachi, Laura; Bonifati, Marco Domenico; Marcello, NorinaPoli, L.; Zedde, Marialuisa; Zini, Andrea; Del Sette, Massimo; Lodigiani, Corrado; Spalloni, Alessandra; Di Lisi, Filomena; Toriello, Antonella; Piras, Valeria; Stilo, Cesare; Tomelleri, Giampaolo; Tancredi, Lucia; Paciaroni, Maurizio; Silvestrelli, Giorgio; Adami, Alessandro; Costa, P.; Morotti, A.; De Giuli, V.; Caria, F.; Gamba, Massimo; Malferrari, Giovanni; Simone, Anna Maria; Musolino, Rossella; Giorli, Elisa; Banfi, Elena; Marcheselli, Simona; Rasura, Maurizia; Pugliese, Nicola; Melis, Maurizio; Bovi, Paolo; Padovani, A.; Burlina, A.; Pezzini, A; Del Zotto, Elisabetta; Giossi, Alessia; Sessa, Maria; Gilberti, Nicola; Magoni, Mauro; Ferrazzi, Paola; Librè, Luca; Rota, Lidia Luciana; Patella, Rosalba; Calabrò, Rocco Salvatore; Bramanti, Placido; La Spina, Paolo; Finocchi, Cinzia; Balestrino, Maurizio; Bruno, Chiara; Massucco, Davide; Gandolfo, Carlo; Traverso, Elisabetta; Delodovici, Maria Luisa; Verrengia, Elena Pinuccia; Carimati, Federico; Bono, Giorgio; Dell'Acqua, Maria Luisa; Bigliardi, Guido; Vandelli, Laura; Nichelli, Paolo Frigio; Carletti, Monica; Cerrato, Paolo; Iacoviello, Licia; Di Castelnuovo, Augusto; de Gaetano, Giovanni; Grassi, Mario; Locatelli, Giampiero; Caso, Valeria; D'Amore, Cataldo; Agnelli, Giancarlo; Checcarelli, Nicoletta; Guidotti, Mario; Arnaboldi, Marco; Giacalone, Giacomo; Zanoli, Elisa; Cavallini, Anna; Persico, Alessandra; Micieli, Giuseppe; Chiti, Alberto; Orlandi, Giovanni; Marchi, Piernicola; Lanari, Alessia; Ciccone, Alfonso; Cucurachi, Laura; Bonifati, Marco Domenico; Marcello, Norin