Articular cartilage,which is mainly composed of collagen Ⅱ,enables smooth skeletal movement.Degeneration of collagen Ⅱ can be caused by various events,such as injury,but degeneration especially increases over the co...Articular cartilage,which is mainly composed of collagen Ⅱ,enables smooth skeletal movement.Degeneration of collagen Ⅱ can be caused by various events,such as injury,but degeneration especially increases over the course of normal aging.Unfortunately,the body does not fully repair itself from this type of degeneration,resulting in impaired movement.Microfracture,an articular cartilage repair surgical technique,has been commonly used in the clinic to induce the repair of tissue at damage sites.Mesenchymal stem cells(MSC)have also been used as cell therapy to repair degenerated cartilage.However,the therapeutic outcomes of all these techniques vary in different patients depending on their age,health,lesion size and the extent of damage to the cartilage.The repairing tissues either form fibrocartilage or go into a hypertrophic stage,both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage.One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC.Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone,or combined with other techniques to greatly assist the therapeutic outcomes.The recent development of human induced pluripotent stem cell(iPSCs),which are able to self-renew and differentiate into multiple cell types,provides a potentially valuable cell resource for drug screening in a“more relevant”cell type.Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.展开更多
Although omics and multi-omics approaches are the most used methods to create signature arrays for liquid biopsy,the high cost of omics technologies still largely limits their wide applications for point-of-care.Inspi...Although omics and multi-omics approaches are the most used methods to create signature arrays for liquid biopsy,the high cost of omics technologies still largely limits their wide applications for point-of-care.Inspired by the bat echolocation mechanism,we propose an“echoes”approach for creating chemiluminescence signatures via screening of a compound library,and serum samples of Alzheimer’s disease(AD)were used for our proof-of-concept study.We first demonstrated the discrepancy in physicochemical properties between AD and healthy control serums.On this basis,we developed a simple,cost-effective,and versatile platform termed UNICODE(UNiversal Interaction of Chemiluminescence echOes for Disease Evaluation).The UNICODE platform consists of a“bat”probe,which generates different chemiluminescence intensities upon interacting with various substrates,and a panel/array of“flag”molecules that are selected from library screening.The UNICODE array could enable the reflecting/“echoing”of the signatures of various serum components and intact physicochemical interactions between serum substrates.In this study,we screened a library of over 1,000 small molecules and identified 12“flag”molecules(top 12)that optimally depict the differences between AD and healthy control serums.Finally,we employed the top 12 array to conduct tests on serum samples and utilized machine learning methods to optimize detection performance.We successfully distinguished AD serums,achieving the highest area under the curve of 90.24%with the random forest method.Our strategy could provide new insights into biofluid abnormality and prototype tools for developing liquid biopsy diagnoses for AD and other diseases.展开更多
文摘Articular cartilage,which is mainly composed of collagen Ⅱ,enables smooth skeletal movement.Degeneration of collagen Ⅱ can be caused by various events,such as injury,but degeneration especially increases over the course of normal aging.Unfortunately,the body does not fully repair itself from this type of degeneration,resulting in impaired movement.Microfracture,an articular cartilage repair surgical technique,has been commonly used in the clinic to induce the repair of tissue at damage sites.Mesenchymal stem cells(MSC)have also been used as cell therapy to repair degenerated cartilage.However,the therapeutic outcomes of all these techniques vary in different patients depending on their age,health,lesion size and the extent of damage to the cartilage.The repairing tissues either form fibrocartilage or go into a hypertrophic stage,both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage.One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC.Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone,or combined with other techniques to greatly assist the therapeutic outcomes.The recent development of human induced pluripotent stem cell(iPSCs),which are able to self-renew and differentiate into multiple cell types,provides a potentially valuable cell resource for drug screening in a“more relevant”cell type.Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.
基金funded by the following:National Institutes of Health grant R01AG055413(NIH,C.R.)National Institutes of Health grant R01AG083759(NIH,C.R.)+4 种基金National Institutes of Health grant R01AG085562(NIH,C.R.)National Institutes of Health grant R21AG059134(NIH,C.R.)National Institutes of Health grant R56AG059814(NIH,C.R.)National Institutes of Health grant R21AG078749(NIH,C.R.)National Institutes of Health grant S10OD028609(NIH,C.R.).
文摘Although omics and multi-omics approaches are the most used methods to create signature arrays for liquid biopsy,the high cost of omics technologies still largely limits their wide applications for point-of-care.Inspired by the bat echolocation mechanism,we propose an“echoes”approach for creating chemiluminescence signatures via screening of a compound library,and serum samples of Alzheimer’s disease(AD)were used for our proof-of-concept study.We first demonstrated the discrepancy in physicochemical properties between AD and healthy control serums.On this basis,we developed a simple,cost-effective,and versatile platform termed UNICODE(UNiversal Interaction of Chemiluminescence echOes for Disease Evaluation).The UNICODE platform consists of a“bat”probe,which generates different chemiluminescence intensities upon interacting with various substrates,and a panel/array of“flag”molecules that are selected from library screening.The UNICODE array could enable the reflecting/“echoing”of the signatures of various serum components and intact physicochemical interactions between serum substrates.In this study,we screened a library of over 1,000 small molecules and identified 12“flag”molecules(top 12)that optimally depict the differences between AD and healthy control serums.Finally,we employed the top 12 array to conduct tests on serum samples and utilized machine learning methods to optimize detection performance.We successfully distinguished AD serums,achieving the highest area under the curve of 90.24%with the random forest method.Our strategy could provide new insights into biofluid abnormality and prototype tools for developing liquid biopsy diagnoses for AD and other diseases.
