Pub Date : 2015-05-13eCollection Date: 2015-01-01DOI: 10.5772/60745
David Lu, Ryon P Graf, Melissa Harvey, Ravi A Madan, Christopher Heery, Jennifer Marte, Sharon Beasley, Kwong Y Tsang, Rachel Krupa, Jessica Louw, Justin Wahl, Natalee Bales, Mark Landers, Dena Marrinucci, Jeffrey Schlom, James L Gulley, Ryan Dittamore
Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed "fresh" via Epic CTC Platform or from "frozen" PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples.
{"title":"Detection and Characterization of Circulating Tumour Cells from Frozen Peripheral Blood Mononuclear Cells.","authors":"David Lu, Ryon P Graf, Melissa Harvey, Ravi A Madan, Christopher Heery, Jennifer Marte, Sharon Beasley, Kwong Y Tsang, Rachel Krupa, Jessica Louw, Justin Wahl, Natalee Bales, Mark Landers, Dena Marrinucci, Jeffrey Schlom, James L Gulley, Ryan Dittamore","doi":"10.5772/60745","DOIUrl":"https://doi.org/10.5772/60745","url":null,"abstract":"<p><p>Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed \"fresh\" via Epic CTC Platform or from \"frozen\" PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-05-05eCollection Date: 2015-01-01DOI: 10.5772/60725
Shannon L Werner, Ryon P Graf, Mark Landers, David T Valenta, Matthew Schroeder, Stephanie B Greene, Natalee Bales, Ryan Dittamore, Dena Marrinucci
The Epic Platform was developed for the unbiased detection and molecular characterization of circulating tumour cells (CTCs). Here, we report assay performance data, including accuracy, linearity, specificity and intra/inter-assay precision of CTC enumeration in healthy donor (HD) blood samples spiked with varying concentrations of cancer cell line controls (CLCs). Additionally, we demonstrate clinical feasibility for CTC detection in a small cohort of metastatic castrate-resistant prostate cancer (mCRPC) patients. The Epic Platform demonstrated accuracy, linearity and sensitivity for the enumeration of all CLC concentrations tested. Furthermore, we established the precision between multiple operators and slide staining batches and assay specificity showing zero CTCs detected in 18 healthy donor samples. In a clinical feasibility study, at least one traditional CTC/mL (CK+, CD45-, and intact nuclei) was detected in 89 % of 44 mCRPC samples, whereas 100 % of samples had CTCs enumerated if additional CTC subpopulations (CK-/CD45- and CK+ apoptotic CTCs) were included in the analysis. In addition to presenting Epic Platform's performance with respect to CTC enumeration, we provide examples of its integrated downstream capabilities, including protein biomarker expression and downstream genomic analyses at single cell resolution.
{"title":"Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization.","authors":"Shannon L Werner, Ryon P Graf, Mark Landers, David T Valenta, Matthew Schroeder, Stephanie B Greene, Natalee Bales, Ryan Dittamore, Dena Marrinucci","doi":"10.5772/60725","DOIUrl":"https://doi.org/10.5772/60725","url":null,"abstract":"<p><p>The Epic Platform was developed for the unbiased detection and molecular characterization of circulating tumour cells (CTCs). Here, we report assay performance data, including accuracy, linearity, specificity and intra/inter-assay precision of CTC enumeration in healthy donor (HD) blood samples spiked with varying concentrations of cancer cell line controls (CLCs). Additionally, we demonstrate clinical feasibility for CTC detection in a small cohort of metastatic castrate-resistant prostate cancer (mCRPC) patients. The Epic Platform demonstrated accuracy, linearity and sensitivity for the enumeration of all CLC concentrations tested. Furthermore, we established the precision between multiple operators and slide staining batches and assay specificity showing zero CTCs detected in 18 healthy donor samples. In a clinical feasibility study, at least one traditional CTC/mL (CK+, CD45-, and intact nuclei) was detected in 89 % of 44 mCRPC samples, whereas 100 % of samples had CTCs enumerated if additional CTC subpopulations (CK-/CD45- and CK+ apoptotic CTCs) were included in the analysis. In addition to presenting Epic Platform's performance with respect to CTC enumeration, we provide examples of its integrated downstream capabilities, including protein biomarker expression and downstream genomic analyses at single cell resolution.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-03-25eCollection Date: 2015-01-01DOI: 10.5772/60522
Lilite Sadovska, Cristina Bajo Santos, Zane Kalniņa, Aija Linē
Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by in vitro studies, it is not entirely clear which of these effects are recapitulated in vivo. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs in vivo and discuss the impact they have, both locally and systemically.
{"title":"Biodistribution, Uptake and Effects Caused by Cancer-Derived Extracellular Vesicles.","authors":"Lilite Sadovska, Cristina Bajo Santos, Zane Kalniņa, Aija Linē","doi":"10.5772/60522","DOIUrl":"10.5772/60522","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by <i>in vitro</i> studies, it is not entirely clear which of these effects are recapitulated <i>in vivo</i>. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs <i>in vivo</i> and discuss the impact they have, both locally and systemically.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-29eCollection Date: 2015-01-01DOI: 10.5772/60126
Shidong Jia, Winston Patrick Kuo
This editorial article summarizes the achievements and current challenges for the Journal of Circulating Biomarkers (JCB) regarding a more strategic approach to branding and attracting a high quality variety of articles. More emphasis is placed on fostering engagement with academic and industry sources operating at the cutting-edge of translational technologies applied to the field of circulating biomarkers (interface between extracellular vesicles including exosomes and microvesicles, circulating tumour cells, cell-free circulating DNA and circulating protein markers) and with those in the investment arena seeking and providing private funding for this area of research.
{"title":"Year of Expanding into Circulating Biomarkers.","authors":"Shidong Jia, Winston Patrick Kuo","doi":"10.5772/60126","DOIUrl":"https://doi.org/10.5772/60126","url":null,"abstract":"<p><p>This editorial article summarizes the achievements and current challenges for the <i>Journal of Circulating Biomarkers</i> (JCB) regarding a more strategic approach to branding and attracting a high quality variety of articles. More emphasis is placed on fostering engagement with academic and industry sources operating at the cutting-edge of translational technologies applied to the field of circulating biomarkers (interface between extracellular vesicles including exosomes and microvesicles, circulating tumour cells, cell-free circulating DNA and circulating protein markers) and with those in the investment arena seeking and providing private funding for this area of research.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This editorial article introduces a renaming of journal Exosomes and Microvesicles (EXMV) to the Journal of Circulating Biomarkers with a new editorial scope, mission and our approach for the upcoming year in relation to engaging at the international level, the translational art of the study of exosomes and microvesicles, and the interface between exosomes and microvesicles, circulating tumor cells, cell-free circulating DNA and circulating protein markers in precision medicine and drug development. There is a slight change in the members of the Editors in Chief, Editorial Board and extending collaborations to international societies, such as the American Society for Exosomes and Microvesicles (ASEMV).
{"title":"New Year, New Name and New Milestones Scope — Journal of Circulating Biomarkers","authors":"S. Jia, W. Kuo","doi":"10.5772/58638","DOIUrl":"https://doi.org/10.5772/58638","url":null,"abstract":"This editorial article introduces a renaming of journal Exosomes and Microvesicles (EXMV) to the Journal of Circulating Biomarkers with a new editorial scope, mission and our approach for the upcoming year in relation to engaging at the international level, the translational art of the study of exosomes and microvesicles, and the interface between exosomes and microvesicles, circulating tumor cells, cell-free circulating DNA and circulating protein markers in precision medicine and drug development. There is a slight change in the members of the Editors in Chief, Editorial Board and extending collaborations to international societies, such as the American Society for Exosomes and Microvesicles (ASEMV).","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/10.5772/58638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973804","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}
Aim: To evaluate the relevance of endothelial-derived apoptotic microparticles (EMPs) with inflammatory cytokine outcomes in patients with ischaemic chronic heart failure (CHF). Methods: A total of 154 patients with moderate-to-severe CHF were enrolled in the study. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-readmission rates were examined. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating EMPs in survivor and non-survivor patient cohorts were 0.286 n/mL (95% CI = 0.271–0.309 n/mL) and 0.673 n/mL (95% CI = 0.65–0.74 n/mL) (P<0.001). There was a significantly lower concentration of sRANKL, OPG, TNF-alpha, sFAS, and sFAS ligand in the survivor patients when compared with those who met composed endpoints. The sFAS/sFAS ligand ratio in the non-survivor patient cohort was significantly higher than in the survivor cohort (P<0.001). In multivariate model EPMs, NYHA class, NT-pro-BNP, TNF-alpha, sFAS/sFAS ligand ratio, and OPG remained statistically significant for the cumulative endpoint: all-cause mortality, CHF-related death, and CHF-related readmission. Conclusion: Increased apoptotic circulating EMPs, OPG, and FAS-sFAS ligand ratio independently predicted cumulative survival in CHF patients.
目的:评价缺血性慢性心力衰竭(CHF)患者内皮源性凋亡微粒(EMPs)与炎症细胞因子预后的相关性。方法:共纳入154例中重度CHF患者。流式细胞术定量emp的数量。检查全因死亡率、冠心病相关死亡率和冠心病再入院率。结果:在中位随访2.18年期间,21名受试者死亡,106名受试者重复住院。幸存者和非幸存者患者队列的循环EMPs中位数分别为0.286 n/mL (95% CI = 0.271-0.309 n/mL)和0.673 n/mL (95% CI = 0.65-0.74 n/mL) (P<0.001)。与满足组成终点的患者相比,存活患者的sRANKL、OPG、tnf - α、sFAS和sFAS配体浓度显著降低。非存活患者队列中sFAS/sFAS配体比例显著高于存活患者队列(P<0.001)。在多变量模型epm中,NYHA分类、nt - probnp、tnf - α、sFAS/sFAS配体比例和OPG在累积终点:全因死亡率、chf相关死亡和chf相关再入院方面仍具有统计学意义。结论:增加的凋亡循环emp、OPG和FAS-sFAS配体比例独立预测CHF患者的累积生存。
{"title":"Apoptotic Microparticles as Predicted Biomarkers in Patients with Chronic Heart Failure — Relevance to Inflammatory Cytokines and Outcomes","authors":"A. Berezin, A. Kremzer, Yulia V. Martovitskaya","doi":"10.5772/60062","DOIUrl":"https://doi.org/10.5772/60062","url":null,"abstract":"Aim: To evaluate the relevance of endothelial-derived apoptotic microparticles (EMPs) with inflammatory cytokine outcomes in patients with ischaemic chronic heart failure (CHF). Methods: A total of 154 patients with moderate-to-severe CHF were enrolled in the study. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-readmission rates were examined. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating EMPs in survivor and non-survivor patient cohorts were 0.286 n/mL (95% CI = 0.271–0.309 n/mL) and 0.673 n/mL (95% CI = 0.65–0.74 n/mL) (P<0.001). There was a significantly lower concentration of sRANKL, OPG, TNF-alpha, sFAS, and sFAS ligand in the survivor patients when compared with those who met composed endpoints. The sFAS/sFAS ligand ratio in the non-survivor patient cohort was significantly higher than in the survivor cohort (P<0.001). In multivariate model EPMs, NYHA class, NT-pro-BNP, TNF-alpha, sFAS/sFAS ligand ratio, and OPG remained statistically significant for the cumulative endpoint: all-cause mortality, CHF-related death, and CHF-related readmission. Conclusion: Increased apoptotic circulating EMPs, OPG, and FAS-sFAS ligand ratio independently predicted cumulative survival in CHF patients.","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/10.5772/60062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70980021","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}
“I have a dream that one day every valley shall be exalted, every hill and mountain shall be made low, the rough places will be made plains, and the crooked places will be made straight, and the glory of the Lord shall be revealed, and all the flesh shall see it together. This is our hope…” (Martin Luther King, Washington D.C., August 28, 1963)
{"title":"“I Have a Dream”","authors":"S. Fais","doi":"10.5772/58709","DOIUrl":"https://doi.org/10.5772/58709","url":null,"abstract":"“I have a dream that one day every valley shall be exalted, every hill and mountain shall be made low, the rough places will be made plains, and the crooked places will be made straight, and the glory of the Lord shall be revealed, and all the flesh shall see it together. This is our hope…” (Martin Luther King, Washington D.C., August 28, 1963)","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/10.5772/58709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70974930","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}
Microvesicles (MVs) are cell-derived vesicles which are of interest in a clinical setting, as they may be predictive of early signs of disease and/or of treatment progression. However, there are growing concerns about using conventional flow cytometry (cFMC) for the detection and quantification of microvesicles. These concerns range from error-sources in collection through to the physical limitations of detection. Here we present a standardized method for collection and analysis which shows that the MV numbers detected by cFCM correlate to donor Body Mass Index (BMI). Although unlikely to be comprehensive, we also demonstrate how cFCM is a useful and valid tool in the analysis of MVs.
{"title":"Protocol Standardization Reveals MV Correlation to Healthy Donor BMI","authors":"P. Hexley, K. Rismiller, C. Robinson, G. Babcock","doi":"10.5772/58527","DOIUrl":"https://doi.org/10.5772/58527","url":null,"abstract":"Microvesicles (MVs) are cell-derived vesicles which are of interest in a clinical setting, as they may be predictive of early signs of disease and/or of treatment progression. However, there are growing concerns about using conventional flow cytometry (cFMC) for the detection and quantification of microvesicles. These concerns range from error-sources in collection through to the physical limitations of detection. Here we present a standardized method for collection and analysis which shows that the MV numbers detected by cFCM correlate to donor Body Mass Index (BMI). Although unlikely to be comprehensive, we also demonstrate how cFCM is a useful and valid tool in the analysis of MVs.","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/10.5772/58527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70972114","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}
I. Vishnubhatla, R. Corteling, Lara Stevanato, C. Hicks, J. Sinden
A successful strategy in regenerative medicine over the last decade has been the translation of stem cell therapy to repair diseased or damaged tissue in a wide range of indications, despite limited evidence attributing any therapeutic benefit to cell survival or differentiation. Recent findings, however, have demonstrated that the conditioned media from stem cell cultures can produce similar efficacious effects compared to those observed for cells. This has led to the stem cell paracrine hypothesis, proposing that secreted factors released from the stem cells contribute significantly to their beneficial effects. It has been well documented that stem cells have the ability to release a range of growth factors, cytokines and chemokines relevant to their function; however, these factors are released at levels too low to account for the reported therapeutic effects. Further purification of the conditioned media has since identified that not only are small molecules released by the stem cells, but so too are a large quantity of membrane-bound vesicles, including exosomes, in a functionally relevant manner. In this review, we present our current understanding and explore the evidence supporting the development of stem cell-derived exosomes as a cell-free regenerative medicine.
{"title":"The Development of Stem Cell-Derived Exosomes as a Cell-Free Regenerative Medicine","authors":"I. Vishnubhatla, R. Corteling, Lara Stevanato, C. Hicks, J. Sinden","doi":"10.5772/58597","DOIUrl":"https://doi.org/10.5772/58597","url":null,"abstract":"A successful strategy in regenerative medicine over the last decade has been the translation of stem cell therapy to repair diseased or damaged tissue in a wide range of indications, despite limited evidence attributing any therapeutic benefit to cell survival or differentiation. Recent findings, however, have demonstrated that the conditioned media from stem cell cultures can produce similar efficacious effects compared to those observed for cells. This has led to the stem cell paracrine hypothesis, proposing that secreted factors released from the stem cells contribute significantly to their beneficial effects. It has been well documented that stem cells have the ability to release a range of growth factors, cytokines and chemokines relevant to their function; however, these factors are released at levels too low to account for the reported therapeutic effects. Further purification of the conditioned media has since identified that not only are small molecules released by the stem cells, but so too are a large quantity of membrane-bound vesicles, including exosomes, in a functionally relevant manner. In this review, we present our current understanding and explore the evidence supporting the development of stem cell-derived exosomes as a cell-free regenerative medicine.","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/10.5772/58597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973738","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}
L. Balaj, F. Momen-Heravi, Weilin Chen, S. Sivaraman, Xuan Zhang, N. Ludwig, E. Meese, T. Wurdinger, D. Noske, A. Charest, F. Hochberg, P. Vandertop, J. Skog, W. Kuo
Essentially, all cells release extracellular vesicles (EVs) that end up in biofluids, including blood, and the contents of these EVs can provide a window into the status of the cells from which they are released. This is particularly interesting in cancer, since these EVs allow for ‘ex-vivo’ analysis of the properties of the tumours without the need for biopsy. Gene mutations, rearrangements, amplifications, and epigenetic changes in the transcriptome can be monitored in circulating EVs. In this study, we used two human tumour cell lines derived from an epidermoid carcinoma and a medulloblastoma, which had amplification for the epidermal growth factor receptor (EGFR) and c-Myc genes, respectively. Cells were implanted subcutaneously into immunocompromised mice, and levels of gene amplification in both groups of subcutaneous tumours were quantified. We then determined if elevated levels of transcripts for the human EGFR and c-Myc were represented in circulating EVs in tumour-bearing mice. The expression levels of both human EGFR (h-EGFR) and human c-Myc (h-c-Myc) mRNAs in circulating EVs correlated well with their amplified status in the tumours. This data provides further support to the idea that circulating EVs are a potential platform for tumour biomarkers.
{"title":"Detection of Human c-Myc and EGFR Amplifications in Circulating Extracellular Vesicles in Mouse Tumour Models","authors":"L. Balaj, F. Momen-Heravi, Weilin Chen, S. Sivaraman, Xuan Zhang, N. Ludwig, E. Meese, T. Wurdinger, D. Noske, A. Charest, F. Hochberg, P. Vandertop, J. Skog, W. Kuo","doi":"10.5772/59174","DOIUrl":"https://doi.org/10.5772/59174","url":null,"abstract":"Essentially, all cells release extracellular vesicles (EVs) that end up in biofluids, including blood, and the contents of these EVs can provide a window into the status of the cells from which they are released. This is particularly interesting in cancer, since these EVs allow for ‘ex-vivo’ analysis of the properties of the tumours without the need for biopsy. Gene mutations, rearrangements, amplifications, and epigenetic changes in the transcriptome can be monitored in circulating EVs. In this study, we used two human tumour cell lines derived from an epidermoid carcinoma and a medulloblastoma, which had amplification for the epidermal growth factor receptor (EGFR) and c-Myc genes, respectively. Cells were implanted subcutaneously into immunocompromised mice, and levels of gene amplification in both groups of subcutaneous tumours were quantified. We then determined if elevated levels of transcripts for the human EGFR and c-Myc were represented in circulating EVs in tumour-bearing mice. The expression levels of both human EGFR (h-EGFR) and human c-Myc (h-c-Myc) mRNAs in circulating EVs correlated well with their amplified status in the tumours. This data provides further support to the idea that circulating EVs are a potential platform for tumour biomarkers.","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70977021","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}