Molecular and cellular therapies最新文献

{"title":"Recruitment and retention of human autologous CD34+ CD117+ CD133+ bone marrow stem cells to infarcted myocardium followed by directed vasculogenesis: Novel strategy for cardiac regeneration.","authors":"Marek Malecki, Chelsea Sabo, Emily Putzer, Chris Stampe, Afsoon Foorohar, Carol Quach, Michael Beauchaine, Xenia Tombokan, Mark Anderson","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Ongoing clinical trials, in regenerative therapy of patients suffering from myocardial infarctions, rely primarily upon administration of bone marrow stem cells to the infarcted zones. Unfortunately, low retention of these cells, to the therapeutic delivery sites, reduces effectiveness of this strategy; thus it has been identified as the most critical problem for advancement of cardiac regenerative medicine.</p><p><strong>Specific aims: </strong>The specific aim of this work was three-fold: (1) to isolate highly viable populations of human, autologous CD34+, CD117+, and CD133+ bone marrow stem cells; (2) to bioengineer heterospecific, tetravalent antibodies and to use them for recruiting of the stem cells to regenerated zones of infarcted myocardium; (3) to direct vasculogenesis of the retained stem cells with the defined factors.</p><p><strong>Patients methods: </strong>Cardiac tissue was biopsied from the hearts of the patients, who were receiving orthotopic heart transplants after multiple cardiac infarctions. This tissue was used to engineer fully human <i>in vitro</i> models of infarcted myocardium. Bone marrow was acquired from these patients. The marrow cells were sorted into populations of cells displaying CD34, CD117, and CD133. Heterospecific, tetravalent antibodies were bioengineered to bridge CD34, CD117, CD133 displayed on the stem cells with cardiac myosin of the infarcted myocardium. The sorted stem cells were administered to the infarcted myocardium in the <i>in vitro</i> models.</p><p><strong>Results: </strong>Administration of the bioengineered, heterospecific antibodies preceding administration of the stem cells greatly improved the stem cells' recruitment and retention to the infarcted myocardium. Treatment of the retained stem cells with vascular endothelial growth factor and angiopoietin efficiently directed their differentiation into endothelial cells, which expressed vascular endothelial cadherin, platelet / endothelial cell adhesion molecule, claudin, and occludin, while forming tight and adherens junctions.</p><p><strong>Conclusions: </strong>This novel strategy improved retention of the patients' autologous bone marrow stem cells to the infarcted myocardium followed by directed vasculogenesis. Therefore, it is worth pursuing it in support of the ongoing clinical trials of cardiac regenerative therapy.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32520869","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}

{"title":"Properties and prospects of adjuvants in influenza vaccination - messy precipitates or blessed opportunities?","authors":"Babak Jalilian, Stig Hill Christiansen, Halldór Bjarki Einarsson, Mehdi Rasoli Pirozyan, Eskild Petersen, Thomas Vorup-Jensen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Influenza is a major challenge to healthcare systems world-wide. While prophylactic vaccination is largely efficient, long-lasting immunity has not been achieved in immunized populations, at least in part due to the challenges arising from the antigen variation between strains of influenza A virus as a consequence of genetic drift and shift. From progress in our understanding of the immune system, the mode-of-action of vaccines can be divided into the stimulation of the adaptive system through inclusion of appropriate vaccine antigens and of the innate immune system by the addition of adjuvant to the vaccine formulation. A shared property of many vaccine adjuvants is found in their nature of water-insoluble precipitates, for instance the particulate material made from aluminum salts. Previously, it was thought that embedding of vaccine antigens in these materials provided a \"depot\" of antigens enabling a long exposure of the immune system to the antigen. However, more recent work points to a role of particulate adjuvants in stimulating cellular parts of the innate immune system. Here, we briefly outline the infectious medicine and immune biology of influenza virus infection and procedures to provide sufficient and stably available amounts of vaccine antigen. This is followed by presentation of the many roles of adjuvants, which involve humoral factors of innate immunity, notably complement. In a perspective of the ultrastructural properties of these humoral factors, it becomes possible to rationalize why these insoluble precipitates or emulsions are such a provocation of the immune system. We propose that the biophysics of particulate material may hold opportunities that could aid the development of more efficient influenza vaccines. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2013-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33372210","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}

{"title":"Flowing through the CRISPR-CAScade: Will genome editing boost cell therapies?","authors":"Uri Ben-David","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent years have seen great advancements in genome editing technologies, allowing for efficient and specific targeting of DNA sequences into the genome. In parallel, advancements in stem cell research, and especially the ability to induce pluripotency in somatic cells, have brought stem cell-derived therapies closer to the clinic. In this commentary, I envision how groundbreaking genome editing technologies will influence stem cell biology research, paving the way to regenerative medicine with genetically engineered cells. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2013-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33372835","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}

{"title":"Molecular and Cellular Therapies: New challenges and opportunities.","authors":"Xiangdong Wang, Dan Peer, Bryon Petersen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gene therapy is suggested to be one of the most specific and efficient modulations for gene deficient diseases and extended to other diseases like cancer and inflammation, even though there are still challenges to be faced, such as specific and selective delivery, minimal to no toxicity, efficient metabolism, simplicity, and measurable efficiency. It is important to identify and validate drug-able disease-specific targets for molecular and cellular therapies, while it is equally important to have disease biomarkers to trace and define the biological effects of molecular and cellular therapies. The importance and significance of allostery in molecular and cellular therapies and \"allosteric disease\", \"allosteric effect\", and \"allosteric drug\" should be more carefully examined and validated. Cell therapy has been attracting an increasing amount of consideration in the development of new treatments for diseases. Molecular and Cellular Therapies (MCT) is a new, open-access journal, devoted to molecular mechanisms, preclinical and clinical research and development of gene-, peptide-, protein-, and cell-based therapies. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2013-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33372834","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}