Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor s...Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable neoplasms.These tumors are highly heterogenous and complex in their nature.Due to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in vivo.Two-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to treatment.Recently,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts.Moreover,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing.In this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current limitations.We will also elaborate on the future implications of these models and their benefit in the clinical setting.展开更多
目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D...目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D细胞培养板,以构建MFC-NIH/3T3共培养多细胞肿瘤球体(CO MCTS);通过活细胞成像表征球体的直径、圆度、面积和透光率;通过激光共聚焦成像表征球体微环境和化疗药物(LipoDOX,5.0μg/ml)的瘤内穿透。结果培养5 d时,两种球体的透光率最低,圆度>0.90,直径约为530μm,面积约为0.23 mm^(2)。两种球体模型内均检测到3种微环境荧光探针分布。LipoDOX能相对均匀地穿透MFC MCTS,却在CO MCTS内表现出外多内少的不均匀穿透,药物荧光强度降低约58.3%(P<0.01)。结论本研究构建了两种具有良好圆度、高紧实度、适中直径和面积的胃癌三维多细胞球体模型,两种胃癌球体模型均表现出酸性、缺氧和氧化还原微环境,可精准、高效地评价化疗药物的瘤内穿透。展开更多
A variety of engineered nanoparticles,including lipid nanoparticles,polymer nanoparticles,gold nanoparticles,and biomimetic nanoparticles,have been studied as delivery vehicles for biomedical applications.When assessi...A variety of engineered nanoparticles,including lipid nanoparticles,polymer nanoparticles,gold nanoparticles,and biomimetic nanoparticles,have been studied as delivery vehicles for biomedical applications.When assessing the efficacy of a nanoparticle-based delivery system,in vitro testing with a model delivery system is crucial because it allows for real-time,in situ quantitative transport analysis,which is often difficult with in vivo animal models.The advent of tissue engineering has offered methods to create experimental models that can closely mimic the 3D microenvironment in the human body.This review paper overviews the types of nanoparticle vehicles,their application areas,and the design strategies to improve delivery efficiency,followed by the uses of engineered microtissues and methods of analysis.In particular,this review highlights studies on multicellular spheroids and other 3D tissue engineering approaches for cancer drug development.The use of bio-engineered tissues can potentially provide low-cost,high-throughput,and quantitative experimental platforms for the development of nanoparticle-based delivery systems.展开更多
文摘Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable neoplasms.These tumors are highly heterogenous and complex in their nature.Due to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in vivo.Two-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to treatment.Recently,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts.Moreover,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing.In this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current limitations.We will also elaborate on the future implications of these models and their benefit in the clinical setting.
基金NSF(CCSS-1809047,CAREER-1653702)NIH(1R01AR072027-01,1R03AR069383-01)the office of undergraduate research(OUR)at the University of Connecticut for providing funds to support this study.
文摘A variety of engineered nanoparticles,including lipid nanoparticles,polymer nanoparticles,gold nanoparticles,and biomimetic nanoparticles,have been studied as delivery vehicles for biomedical applications.When assessing the efficacy of a nanoparticle-based delivery system,in vitro testing with a model delivery system is crucial because it allows for real-time,in situ quantitative transport analysis,which is often difficult with in vivo animal models.The advent of tissue engineering has offered methods to create experimental models that can closely mimic the 3D microenvironment in the human body.This review paper overviews the types of nanoparticle vehicles,their application areas,and the design strategies to improve delivery efficiency,followed by the uses of engineered microtissues and methods of analysis.In particular,this review highlights studies on multicellular spheroids and other 3D tissue engineering approaches for cancer drug development.The use of bio-engineered tissues can potentially provide low-cost,high-throughput,and quantitative experimental platforms for the development of nanoparticle-based delivery systems.
