Mesenchymal stem/stromal cells(MSCs)have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace th...Mesenchymal stem/stromal cells(MSCs)have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace the injured/diseased tissue,it is now accepted that these cells secrete factors to promote tissue repair.1 Among these factors,small extracellular vesicles(sEVs)of size 50–200 nm,which include the exosomes,have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs.2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models,as recently reviewed.3 However,the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.展开更多
Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of e...Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of earlier detection. While liquid biopsy is a promising alternative to tissue biopsy, it has its challenges and limitations. A major challenge is the isolation of bona fide lipid membrane vesicles from biological fluids. In this review, we presented a new perspective of isolating different types of extracellular vesicles (EVs) by their affinity for membrane lipid binding ligands for liquid biopsy. EVs are lipid membrane particles naturally released by almost all cells and are found in almost all biological fluids suitable for liquid biopsy. They carry materials from the secreting cells that could affect the biology of the recipient cells and could thus inform on the state and progress of the disease. However, isolating bona fide EVs is a technical challenge as biological fluids have a complex composition and contain particles or aggregates that are physically similar to EVs. Here we review the use of membrane lipid-binding ligands to isolate different bona fide EV subtypes, and to circumvent the problem of co-isolating physically similar non-EV complexes in current EV isolation protocols. We will discuss the advantages of this technique and its potential for accelerated biomarker discovery and validation through examples of pre-clinical studies. We propose that isolating EV subtypes is a technically viable and robust strategy to overcome the current bottleneck of isolating EVs for liquid biopsy.展开更多
基金This work was funded by National University of Singapore(No.R221000114114,R221000134114)National Medical Research Council Singapore(No.R221000123213)SKL and WST are supported by the Agency for Science,Technology and Research under its Health and Biomedical Sciences Industry Alignment Fund Pre-Positioning(No.H19H6a0026).
文摘Mesenchymal stem/stromal cells(MSCs)have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace the injured/diseased tissue,it is now accepted that these cells secrete factors to promote tissue repair.1 Among these factors,small extracellular vesicles(sEVs)of size 50–200 nm,which include the exosomes,have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs.2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models,as recently reviewed.3 However,the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.
文摘Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of earlier detection. While liquid biopsy is a promising alternative to tissue biopsy, it has its challenges and limitations. A major challenge is the isolation of bona fide lipid membrane vesicles from biological fluids. In this review, we presented a new perspective of isolating different types of extracellular vesicles (EVs) by their affinity for membrane lipid binding ligands for liquid biopsy. EVs are lipid membrane particles naturally released by almost all cells and are found in almost all biological fluids suitable for liquid biopsy. They carry materials from the secreting cells that could affect the biology of the recipient cells and could thus inform on the state and progress of the disease. However, isolating bona fide EVs is a technical challenge as biological fluids have a complex composition and contain particles or aggregates that are physically similar to EVs. Here we review the use of membrane lipid-binding ligands to isolate different bona fide EV subtypes, and to circumvent the problem of co-isolating physically similar non-EV complexes in current EV isolation protocols. We will discuss the advantages of this technique and its potential for accelerated biomarker discovery and validation through examples of pre-clinical studies. We propose that isolating EV subtypes is a technically viable and robust strategy to overcome the current bottleneck of isolating EVs for liquid biopsy.
