Background & Objective: Despite the great effort spent over recent decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them still remain unclear. In particular, the study of rare CNS diseases is hampered by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality. The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue have allowed the modeling of several neurological diseases “in a dish” and have also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting. In recent years, the development of induced pluripotent stem cell (iPS) technology has added enormous value to the aforementioned approach, thanks to their capability for generating disease-relevant cell phenotypes in vitro and to their perspective use in autologous transplantation. However, while the potentiality of ESC, NSC and iPS has been widely sponsored, the pitfalls related to the available protocols for differentiation and the heterogeneity of lines deriving from different individuals have been poorly discussed. Here we present pro and contra of using ESC, NSC or iPS for modeling rare diseases like Lysosomal Storage disorders and Motor Neuron Diseases. Conclusion: In this view, the advent of gene editing technologies is a unique opportunity to standardize the data analysis in preclinical studies and to tailor clinical protocols for stem cell-mediated therapy.

De Filippis, L., Zalfa, C., Ferrari, D. (2017). Neural stem cells and human induced pluripotent stem cells to model rare CNS diseases. CNS & NEUROLOGICAL DISORDERS. DRUG TARGETS, 16(8), 915-926 [10.2174/1871527316666170615121753].

Neural stem cells and human induced pluripotent stem cells to model rare CNS diseases

De Filippis, L
;
Zalfa, C;Ferrari, D
2017

Abstract

Background & Objective: Despite the great effort spent over recent decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them still remain unclear. In particular, the study of rare CNS diseases is hampered by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality. The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue have allowed the modeling of several neurological diseases “in a dish” and have also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting. In recent years, the development of induced pluripotent stem cell (iPS) technology has added enormous value to the aforementioned approach, thanks to their capability for generating disease-relevant cell phenotypes in vitro and to their perspective use in autologous transplantation. However, while the potentiality of ESC, NSC and iPS has been widely sponsored, the pitfalls related to the available protocols for differentiation and the heterogeneity of lines deriving from different individuals have been poorly discussed. Here we present pro and contra of using ESC, NSC or iPS for modeling rare diseases like Lysosomal Storage disorders and Motor Neuron Diseases. Conclusion: In this view, the advent of gene editing technologies is a unique opportunity to standardize the data analysis in preclinical studies and to tailor clinical protocols for stem cell-mediated therapy.
Articolo in rivista - Articolo scientifico
Alzheimer’s disease; Amyotrophic Lateral Sclerosis; Central nervous system; Disease modeling; Embryonic stem cells; Enzyme replacement therapy; Glycosaminoglycans; Huntington’s disease; Iduronate 2-Sulfatase; Induced pluripotent cells; Lysosomal storage diseases; Motor Neuron diseases; Mucopolysaccharidosis; Mucopolysaccharidosis Type II or Huner Syndrome; Neural stem cells; Neurological disorders; Parkinson’s disease; Rare CNS diseases; Spinal cord; Stem cells; Sub-granular Zone; Sub-Ventricular zone; Neuroscience (all); Pharmacology
English
2017
16
8
915
926
none
De Filippis, L., Zalfa, C., Ferrari, D. (2017). Neural stem cells and human induced pluripotent stem cells to model rare CNS diseases. CNS & NEUROLOGICAL DISORDERS. DRUG TARGETS, 16(8), 915-926 [10.2174/1871527316666170615121753].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/191957
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