J. Lötvall, J. Skog, A. Vlassov, A. Sacido, E. Rohde, J. Gere, W. Kuo
Extracellular vesicles (EVs), including exosomes and microvesicles, carry a variety of bio-macromolecules, including mRNA, microRNA, other non-coding RNAs, proteins and lipids. EVs have emerged as a promising, minimally invasive (liquid biopsies) and novel source of material for molecular diagnostics, and may provide a surrogate to tissue biopsy-based biomarkers for a variety of diseases. Although EVs can be easily identified and collected from biological fluids using commercial kits, further research and proper validation is needed in order for them to be useful in the clinical setting. Currently, several EV-based research and diagnostic companies have developed research-based kits and are in the process of working with clinical laboratories to develop and validate EV-based assays for a variety of diseases. The successful clinical application of EV-based diagnostic assays will require close collaboration between industry, academia, regulatory agencies and access to patient samples. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for EV-based diagnostics. We recognize that the EV field offers new promise for personalized/precision medicine and targeted treatment in a variety of diseases. A short course was held as a four-session webinar series in September and October 2014, presented by pioneers and experts in the EV domain, covering a broad range of topics from an overview of the field to its applications, and the current state and challenges of the commercialization of EVs for research and an introduction to the clinic. It was concluded with a panel discussion on the regulatory aspects and funding opportunities in this field. A summary of the short course is presented as a meeting dispatch.
{"title":"Short Course in Extracellular Vesicles — The Transition from Tissue to Liquid Biopsies","authors":"J. Lötvall, J. Skog, A. Vlassov, A. Sacido, E. Rohde, J. Gere, W. Kuo","doi":"10.5772/60053","DOIUrl":"https://doi.org/10.5772/60053","url":null,"abstract":"Extracellular vesicles (EVs), including exosomes and microvesicles, carry a variety of bio-macromolecules, including mRNA, microRNA, other non-coding RNAs, proteins and lipids. EVs have emerged as a promising, minimally invasive (liquid biopsies) and novel source of material for molecular diagnostics, and may provide a surrogate to tissue biopsy-based biomarkers for a variety of diseases. Although EVs can be easily identified and collected from biological fluids using commercial kits, further research and proper validation is needed in order for them to be useful in the clinical setting. Currently, several EV-based research and diagnostic companies have developed research-based kits and are in the process of working with clinical laboratories to develop and validate EV-based assays for a variety of diseases. The successful clinical application of EV-based diagnostic assays will require close collaboration between industry, academia, regulatory agencies and access to patient samples. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for EV-based diagnostics. We recognize that the EV field offers new promise for personalized/precision medicine and targeted treatment in a variety of diseases. A short course was held as a four-session webinar series in September and October 2014, presented by pioneers and experts in the EV domain, covering a broad range of topics from an overview of the field to its applications, and the current state and challenges of the commercialization of EVs for research and an introduction to the clinic. It was concluded with a panel discussion on the regulatory aspects and funding opportunities in this field. A summary of the short course is presented as a meeting dispatch.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70979762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johan Ankarklev, D. Hjelmqvist, Pierre-Yves Mantel
Investigation of the involvement of extracellular vesicles (EVs) in parasite biology has burgeoned in recent years. Human infecting protozoan parasites, such as Trypanosoma cruzi, Lesihmania sp. and Trichomonas vaginalis, have all demonstrated the utilization of EVs as virulence factors in order to activate or hamper host immunity. Novel findings have provided evidence that the deployment of EVs by Plasmodium sp. has a major impact in disease outcomes and serves as an integral part in controlling stage switching in its life cycle. Clinical studies have highlighted elevated levels of EVs in patients with severe malaria disease and EVs have been linked to increased sequestration of infected red blood cells to the endothelium, causing obstruction of blood flow. It has also been found that EVs produced during malaria disease activate innate immunity. Intriguingly, recent discoveries indicate that Plasmodium sp. “highjack” the erythrocyte microvesiculation system in order to cross-communicate. Both the transfer of DNA and parasite density regulation has been suggested as key mechanisms of EVs in malaria biology.
{"title":"Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication","authors":"Johan Ankarklev, D. Hjelmqvist, Pierre-Yves Mantel","doi":"10.5772/58596","DOIUrl":"https://doi.org/10.5772/58596","url":null,"abstract":"Investigation of the involvement of extracellular vesicles (EVs) in parasite biology has burgeoned in recent years. Human infecting protozoan parasites, such as Trypanosoma cruzi, Lesihmania sp. and Trichomonas vaginalis, have all demonstrated the utilization of EVs as virulence factors in order to activate or hamper host immunity. Novel findings have provided evidence that the deployment of EVs by Plasmodium sp. has a major impact in disease outcomes and serves as an integral part in controlling stage switching in its life cycle. Clinical studies have highlighted elevated levels of EVs in patients with severe malaria disease and EVs have been linked to increased sequestration of infected red blood cells to the endothelium, causing obstruction of blood flow. It has also been found that EVs produced during malaria disease activate innate immunity. Intriguingly, recent discoveries indicate that Plasmodium sp. “highjack” the erythrocyte microvesiculation system in order to cross-communicate. Both the transfer of DNA and parasite density regulation has been suggested as key mechanisms of EVs in malaria biology.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Campanella, C. C. Bavisotto, A. M. Gammazza, D. Nikolić, F. Rappa, S. David, F. Cappello, F. Bucchieri, S. Fais
Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.
{"title":"Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-Cell Communication","authors":"C. Campanella, C. C. Bavisotto, A. M. Gammazza, D. Nikolić, F. Rappa, S. David, F. Cappello, F. Bucchieri, S. Fais","doi":"10.5772/58721","DOIUrl":"https://doi.org/10.5772/58721","url":null,"abstract":"Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70974610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Anile, C. Chiappetta, D. Diso, V. Liparulo, M. Leopizzi, C. Della Rocca, F. Venuta
Objectives: Metastatic recurrence is the most frequent cause of death after surgical resection of lung cancer. Manipulation during surgery has been advocated as one of the causes contributing to promotion of spreading. Methods: We investigated if the detection of plasma circulating free DNA (cfDNA) is influenced by surgical manipulation in 25 lung cancer patients (17 males and eight females) undergoing complete resection; 20 health subjects formed the control group. Bloodstream levels of cfDNA were detected before surgery, one week and one month after surgery. Results: CfDNA levels measured preoperatively and in the control group were 23 07 ± 7 4 ng/mL and 7 5 ± 3 4 ng/mL respectively (p=0 0002); levels at one week and one month were 68 2 ± 36 2 ng/mL and 9 6 ± 3 1 ng/mL respectively. The difference between the three time points were statistically significant (preop vs. one week p=0 0006; one week vs. one month p=0 0003) with an increase in the first week and a strong decrease after one month. CfDNA levels at one month were not statistically different from those recorded in the control group. There was no correlation between preoperative cfDNA levels, tumour stage, grading and histology and patient demographics. No correlation was found between postoperative cfDNA, type of surgical procedure, histology and stage. After a median follow-up of 16 months no recurrence was detected. Conclusions: Surgical manipulation determines increased cfDNA levels in the early postoperative period; however, after one month they decrease within the normal range, at levels that are statistically comparable with healthy subjects.
{"title":"Influence of Lung Parenchyma Surgical Manipulation on Circulating Free DNA","authors":"M. Anile, C. Chiappetta, D. Diso, V. Liparulo, M. Leopizzi, C. Della Rocca, F. Venuta","doi":"10.5772/59875","DOIUrl":"https://doi.org/10.5772/59875","url":null,"abstract":"Objectives: Metastatic recurrence is the most frequent cause of death after surgical resection of lung cancer. Manipulation during surgery has been advocated as one of the causes contributing to promotion of spreading. Methods: We investigated if the detection of plasma circulating free DNA (cfDNA) is influenced by surgical manipulation in 25 lung cancer patients (17 males and eight females) undergoing complete resection; 20 health subjects formed the control group. Bloodstream levels of cfDNA were detected before surgery, one week and one month after surgery. Results: CfDNA levels measured preoperatively and in the control group were 23 07 ± 7 4 ng/mL and 7 5 ± 3 4 ng/mL respectively (p=0 0002); levels at one week and one month were 68 2 ± 36 2 ng/mL and 9 6 ± 3 1 ng/mL respectively. The difference between the three time points were statistically significant (preop vs. one week p=0 0006; one week vs. one month p=0 0003) with an increase in the first week and a strong decrease after one month. CfDNA levels at one month were not statistically different from those recorded in the control group. There was no correlation between preoperative cfDNA levels, tumour stage, grading and histology and patient demographics. No correlation was found between postoperative cfDNA, type of surgical procedure, histology and stage. After a median follow-up of 16 months no recurrence was detected. Conclusions: Surgical manipulation determines increased cfDNA levels in the early postoperative period; however, after one month they decrease within the normal range, at levels that are statistically comparable with healthy subjects.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/59875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70978081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolyn D. Roberson, Ç. Gerçel-Taylor, Ying Qi, K. Schey, D. Taylor
Altered tumour antigens can initiate cellular and humoral immune responses; however, they often fail to eliminate tumours. In humans, the presence of cancer is generally associated with the suppression of T cell activation and effector responses, characterized as a Th1 to Th2 biased response. This Th2 response leads to the production of tumour-reactive antibodies. Further, neoplastic lesions and biological fluids of cancer patients contain an abundance of tumour-derived exosomes (TDE) expressing tumour antigens. Expression of tumour antigens on TDE may represent an antibody target and serve to block antibody binding to the tumour, implicating a role for these nanovesicles in tumour survival. In this study, ovarian tumour cell proteins were separated by two-dimensional electrophoresis (2-DE) and patient-derived antibodies were used to analyse immunoreactivity. Common immunoreactive proteins among ovarian cancer patients were identified by mass spectrometry and six proteins were selected based on recognition and correlation with cancer pathogenesis. The identity of these proteins were confirmed by immunoreactivity of patient-derived antibodies with recombinant proteins and their presence on in vivo and in vitro-derived ovarian tumour exosomes was defined. Analysis of the TDE demonstrated bound tumour-reactive immunoglobulins, exhibiting immunoreactivity with specific antigens, suggesting that patient-derived antibodies recognize tumour antigens on circulating exosomes.
{"title":"Identification of Immunoreactive Tumour Antigens Using Free and Exosome-Associated Humoral Responses","authors":"Carolyn D. Roberson, Ç. Gerçel-Taylor, Ying Qi, K. Schey, D. Taylor","doi":"10.5772/57524","DOIUrl":"https://doi.org/10.5772/57524","url":null,"abstract":"Altered tumour antigens can initiate cellular and humoral immune responses; however, they often fail to eliminate tumours. In humans, the presence of cancer is generally associated with the suppression of T cell activation and effector responses, characterized as a Th1 to Th2 biased response. This Th2 response leads to the production of tumour-reactive antibodies. Further, neoplastic lesions and biological fluids of cancer patients contain an abundance of tumour-derived exosomes (TDE) expressing tumour antigens. Expression of tumour antigens on TDE may represent an antibody target and serve to block antibody binding to the tumour, implicating a role for these nanovesicles in tumour survival. In this study, ovarian tumour cell proteins were separated by two-dimensional electrophoresis (2-DE) and patient-derived antibodies were used to analyse immunoreactivity. Common immunoreactive proteins among ovarian cancer patients were identified by mass spectrometry and six proteins were selected based on recognition and correlation with cancer pathogenesis. The identity of these proteins were confirmed by immunoreactivity of patient-derived antibodies with recombinant proteins and their presence on in vivo and in vitro-derived ovarian tumour exosomes was defined. Analysis of the TDE demonstrated bound tumour-reactive immunoglobulins, exhibiting immunoreactivity with specific antigens, suggesting that patient-derived antibodies recognize tumour antigens on circulating exosomes.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/57524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70967192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This editorial article introduces the new scientific journal Exosomes and Microvesicles (EXMV), the official journal of the American Society for Exosomes and Microvesicles (ASEMV), and describes its editorial line and mission in relation to the role of the Society, the state of the art of the study of exosomes and microvesicles, and the overall approach of the publication.
{"title":"Announcing Exosomes and Microvesicles, the Official Journal of the American Society for Exosomes and Microvesicles","authors":"S. Gould, D. Taylor, A. Chiesi, W. Kuo","doi":"10.5772/56520","DOIUrl":"https://doi.org/10.5772/56520","url":null,"abstract":"This editorial article introduces the new scientific journal Exosomes and Microvesicles (EXMV), the official journal of the American Society for Exosomes and Microvesicles (ASEMV), and describes its editorial line and mission in relation to the role of the Society, the state of the art of the study of exosomes and microvesicles, and the overall approach of the publication.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Hendrix, C. Ciccone, C. Gespach, M. Bracke, O. De Wever, W. Westbroek
The secretory Rab27B small GTPase promotes invasive growth, tumourigenicity and metastasis in oestrogen receptor (ER)-positive human breast cancer cells. Coherently, increased Rab27B expression in breast cancer patients is associated with a poor prognosis. In the present study, bio-energetic profiling revealed that oxidative phosphorylation is significantly reduced in ER-positive breast cancer cells engineered to overexpress Rab27B levels as observed in invasive clinical primary breast cancer. Rab27B-induced metabolic reprogramming to aerobic glycolysis was further evidenced by increased extracellular acidification followed by cathepsin B activation and doxorubicin resistance. Transient silencing of Rab27B and stable transfection of Rab27A, and Rab27B mutants in ER-positive breast cancer cells confirmed that this response was Rab27B-specific and dependent upon Rab27B-GTP activation and vesicle membrane attachment through the C-terminal geranylgeranyl group of this small GTPase. Rab27B-driven extracellular acidification is required and is sufficient to induce filopodia-like morphological changes, primarily involved in the process of cancer cell invasion. Our data demonstrate that a Rab27B-dependent switch from oxidative phosphorylation towards aerobic glycolysis in ER-positive breast cancer cells is accompanied by acidification of the tumour environment.
{"title":"Rab27B-Mediated Metabolic Reprogramming Induces Secretome Acidification and Chemoresistance in Breast Cancer Cells","authors":"A. Hendrix, C. Ciccone, C. Gespach, M. Bracke, O. De Wever, W. Westbroek","doi":"10.5772/56521","DOIUrl":"https://doi.org/10.5772/56521","url":null,"abstract":"The secretory Rab27B small GTPase promotes invasive growth, tumourigenicity and metastasis in oestrogen receptor (ER)-positive human breast cancer cells. Coherently, increased Rab27B expression in breast cancer patients is associated with a poor prognosis. In the present study, bio-energetic profiling revealed that oxidative phosphorylation is significantly reduced in ER-positive breast cancer cells engineered to overexpress Rab27B levels as observed in invasive clinical primary breast cancer. Rab27B-induced metabolic reprogramming to aerobic glycolysis was further evidenced by increased extracellular acidification followed by cathepsin B activation and doxorubicin resistance. Transient silencing of Rab27B and stable transfection of Rab27A, and Rab27B mutants in ER-positive breast cancer cells confirmed that this response was Rab27B-specific and dependent upon Rab27B-GTP activation and vesicle membrane attachment through the C-terminal geranylgeranyl group of this small GTPase. Rab27B-driven extracellular acidification is required and is sufficient to induce filopodia-like morphological changes, primarily involved in the process of cancer cell invasion. Our data demonstrate that a Rab27B-dependent switch from oxidative phosphorylation towards aerobic glycolysis in ER-positive breast cancer cells is accompanied by acidification of the tumour environment.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/56521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Romagnoli, P. A. Toniolo, Isabela Katz Migliori, E. Caldini, M. A. Ferreira, C. R. Pizzo, P. C. Bergami-Santos, J. Barbuto
Exosomes (Exos) are secreted nanovesicles that contain membrane proteins and genetic material, which can be transferred between cells and contribute to their communication in the body. We show that Exos, obtained from mature human dendritic cells (DCs), are incorporated by tumour cells, which after Exos treatment, acquire the expression of HLA-class I, HLA-class II, CD86, CD11c, CD54 and CD18. This incorporation reaches its peak eight hours after treatment, can be observed in different cell tumour lines (SK-BR-3, U87 and K562) and could be a means to transform non-immunogenic into immunogenic tumour cells. Interestingly, tetraspanins, which are expressed by the tumour cells, have their surface level decreased after Exo treatment. Furthermore, the intensity of Exo incorporation by the different tumour cell lines was proportional to their CD9 expression levels and pre-treatment of Exos with anti-CD9 decreased their incorporation (by SK-BR-3 cells). This modification of tumour cells by DC-derived Exos may allow their use in new immunotherapeutic approaches to cancer. Furthermore, by showing the involvement of CD9 in this incorporation, we provide a possible selection criterion for tumours to be addressed by this strategy.
{"title":"Tumour Cells Incorporate Exosomes Derived from Dendritic Cells through a Mechanism Involving the Tetraspanin CD9","authors":"G. Romagnoli, P. A. Toniolo, Isabela Katz Migliori, E. Caldini, M. A. Ferreira, C. R. Pizzo, P. C. Bergami-Santos, J. Barbuto","doi":"10.5772/52069","DOIUrl":"https://doi.org/10.5772/52069","url":null,"abstract":"Exosomes (Exos) are secreted nanovesicles that contain membrane proteins and genetic material, which can be transferred between cells and contribute to their communication in the body. We show that Exos, obtained from mature human dendritic cells (DCs), are incorporated by tumour cells, which after Exos treatment, acquire the expression of HLA-class I, HLA-class II, CD86, CD11c, CD54 and CD18. This incorporation reaches its peak eight hours after treatment, can be observed in different cell tumour lines (SK-BR-3, U87 and K562) and could be a means to transform non-immunogenic into immunogenic tumour cells. Interestingly, tetraspanins, which are expressed by the tumour cells, have their surface level decreased after Exo treatment. Furthermore, the intensity of Exo incorporation by the different tumour cell lines was proportional to their CD9 expression levels and pre-treatment of Exos with anti-CD9 decreased their incorporation (by SK-BR-3 cells). This modification of tumour cells by DC-derived Exos may allow their use in new immunotherapeutic approaches to cancer. Furthermore, by showing the involvement of CD9 in this incorporation, we provide a possible selection criterion for tumours to be addressed by this strategy.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/52069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70935805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. Suntres, Milton G. Smith, F. Momen-Heravi, Jie Hu, Xin Zhang, Ying Wu, Hongguang Zhu, Jiping Wang, Jian Zhou, W. Kuo
Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.
{"title":"Therapeutic Uses of Exosomes","authors":"Z. Suntres, Milton G. Smith, F. Momen-Heravi, Jie Hu, Xin Zhang, Ying Wu, Hongguang Zhu, Jiping Wang, Jian Zhou, W. Kuo","doi":"10.5772/56522","DOIUrl":"https://doi.org/10.5772/56522","url":null,"abstract":"Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/56522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mesenchymal stem cell (MSC) has just been approved as the first “off-the-shelf” stem cell pharmaceutical drug with an anticipation of more approvals following completion of numerous rigorous clinical trials. Despite this progress, the rationale for MSC therapeutic efficacy remains tenuous and is increasingly rationalized on a secretion rather than differentiation mechanism. Recent studies identifying exosome as the secreted agent mediating MSC therapeutic efficacy could potentially reduce a cell-based drug to a safer biologic-based alternative. Here we review the development of MSC exosome as a potential first-in-class therapeutic, and the unique challenges in the manufacture and regulatory oversight of this new class of therapeutics.
{"title":"Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell","authors":"R. Yeo, R. C. Lai, K. Tan, S. Lim","doi":"10.5772/57460","DOIUrl":"https://doi.org/10.5772/57460","url":null,"abstract":"Mesenchymal stem cell (MSC) has just been approved as the first “off-the-shelf” stem cell pharmaceutical drug with an anticipation of more approvals following completion of numerous rigorous clinical trials. Despite this progress, the rationale for MSC therapeutic efficacy remains tenuous and is increasingly rationalized on a secretion rather than differentiation mechanism. Recent studies identifying exosome as the secreted agent mediating MSC therapeutic efficacy could potentially reduce a cell-based drug to a safer biologic-based alternative. Here we review the development of MSC exosome as a potential first-in-class therapeutic, and the unique challenges in the manufacture and regulatory oversight of this new class of therapeutics.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/57460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70966248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}