Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regen...Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.展开更多
Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the ga...Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the gap between traditional two-dimensional(2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition,3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.展开更多
Nanomedicine involves the use of engineered nanoscale materials in an extensive range of diagnostic and therapeutic applications and can be applied to the treatment of many diseases.Despite the rapid progress and trem...Nanomedicine involves the use of engineered nanoscale materials in an extensive range of diagnostic and therapeutic applications and can be applied to the treatment of many diseases.Despite the rapid progress and tremendous potential of nanomedicine in the past decades,the clinical translational process is still quite slow,owing to the difficulty in understanding,evaluating,and predicting nanomaterial behaviors within the complex environment of human beings.Microfluidics-based organ-on-a-chip(Organ Chip)techniques offer a promising way to resolve these challenges.Sophisticatedly designed Organ Chip enable in vitro simulation of the in vivo microenvironments,thus providing robust platforms for evaluating nanomedicine.Herein,we review recent developments and achievements in Organ Chip models for nanomedicine evaluations,categorized into seven broad sections based on the target organ systems:respiratory,digestive,lymphatic,excretory,nervous,and vascular,as well as coverage on applications relating to cancer.We conclude by providing our perspectives on the challenges and potential future directions for applications of Organ Chip in nanomedicine.展开更多
基金funded by the National Natural Science Foundation of China(81771125,81471803,81671031)the Sichuan Province Youth Science and Technology Innovation Team(2014TD0001)
文摘Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.
基金supported by the National Megaprojects for Infectious Diseases (2014ZX10004002-004001)
文摘Three-dimensional(3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover,these models bridge the gap between traditional two-dimensional(2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition,3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.
基金National Natural Science Foundation of China for Innovative Research Groups(No.51621002)Y.S.Z.was not supported by this fundinstead,support by the Brigham Research Institute is thanked.We acknowledge Dr.Amy Wen and Ms.Xuewei Zhang for helpful discussion.Any opinions,findings,conclusions,or recommendations expressed herein are those of the author(s).
文摘Nanomedicine involves the use of engineered nanoscale materials in an extensive range of diagnostic and therapeutic applications and can be applied to the treatment of many diseases.Despite the rapid progress and tremendous potential of nanomedicine in the past decades,the clinical translational process is still quite slow,owing to the difficulty in understanding,evaluating,and predicting nanomaterial behaviors within the complex environment of human beings.Microfluidics-based organ-on-a-chip(Organ Chip)techniques offer a promising way to resolve these challenges.Sophisticatedly designed Organ Chip enable in vitro simulation of the in vivo microenvironments,thus providing robust platforms for evaluating nanomedicine.Herein,we review recent developments and achievements in Organ Chip models for nanomedicine evaluations,categorized into seven broad sections based on the target organ systems:respiratory,digestive,lymphatic,excretory,nervous,and vascular,as well as coverage on applications relating to cancer.We conclude by providing our perspectives on the challenges and potential future directions for applications of Organ Chip in nanomedicine.
