作者: Daniel Simão , Francisca Arez , Ana P. Terasso , Catarina Pinto , Marcos F. Q. Sousa
关键词: Cellular differentiation 、 Neuroscience 、 Neurogenesis 、 Biology 、 Neurotrophic factors 、 Neural stem cell 、 Context (language use) 、 Cell culture 、 Induced pluripotent stem cell 、 Cell aggregation
摘要: Therapeutic breakthroughs in neurological disorders have been hampered by the lack of accurate central nervous system (CNS) models. The development these models allows study disease onset/progression mechanisms and preclinical evaluation new therapeutics. This has traditionally relied on genetically engineered animal that often diverge considerably from human phenotype (developmental, anatomic, physiological) 2D vitro cell models, which fail to recapitulate characteristics target tissue (cell-cell cell-matrix interactions, polarity, etc.). Recapitulation CNS phenotypic functional features requires implementation advanced culture strategies, such as 3D systems, enable mimic vivo structural molecular complexity. Models based differentiation neural stem cells (hNSC) cultures great potential complementary tools research, bridging gap between clinical studies robust scalable processes for hNSC can improve accuracy early stage research. In this context, use software-controlled stirred-tank bioreactors (STB) provides an efficient technological platform aggregation differentiation. enables monitor control important physicochemical parameters culture, dissolved oxygen. Importantly, adoption a perfusion operation mode stable flow nutrients differentiation/neurotrophic factors, while clearing toxic by-products. contributes setting closer physiological, mimicking microenvironment. chapter, we address technical requirements procedures strategies hNSC, operating STB under long-term cultures. strategy is suitable generation be used feed high-throughput screening platforms, contributing expand available drug toxicological studies.