{"71346":{"#nid":"71346","#data":{"type":"news","title":"Molecule Delivery Method Improves Embryonic Stem Cell Differentiation","body":[{"value":"\u003Cp\u003EEmbryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. However, the inability of stem cells to efficiently develop into the desired specific cell type - such as muscle, skin, blood vessels, bone or neurons - now limits the potential clinical utility of this therapy.\u003C\/p\u003E\n\u003Cp\u003ENew research shows that delivering molecules within aggregates of embryonic stem cells via biodegradable microspheres enhances the efficiency and purity of differentiation, which is the process the cells undergo to become more specialized. Details of the microsphere-mediated delivery method, which is funded by the National Science Foundation, were presented on April 9 at the 235th American Chemical Society national meeting. \n\u003C\/p\u003E\n\u003Cp\u003E\u0022Directing embryonic stem cells to efficiently differentiate into a specific cell type has been challenging to this point,\u0022 said Todd McDevitt, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. \u0022In my lab, we\u0027re trying to better define and then control the environmental cues that regulate the fate and function of the stem cells.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EBecause physical interactions between stem cells is critical during normal embryonic development, most laboratory growth methods allow the cells to aggregate in three-dimensional clumps called \u0027embryoid bodies\u0027 in order to differentiate. After individual cells aggregate together, hollow internal structures begin to develop and the aggregate becomes larger and more complex over time.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022Many researchers add soluble factors to the culture dish medium to direct differentiation, but this does not accurately mimic the time and location of signaling events present in normal development, and may contribute to heterogeneous differentiation,\u0022 said McDevitt. \u0022Our method focuses on incorporating the differentiation factors directly into the cell aggregates in order to have a more controlled mechanism of presentation.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EThe research team - which also includes graduate students Richard Carpenedo and Andres Bratt-Leal and undergraduate students Ross Marklein and Scott Seaman - fabricated biodegradable polymer microspheres that could contain growth factors, proteins or other small molecules.\n\u003C\/p\u003E\n\u003Cp\u003EMcDevitt\u0027s team tested the impact of the poly(lactic-co-glycolic acid) (PLGA) microspheres on embryonic stem cell differentiation under different conditions by varying the microsphere-to-cell ratio and speed at which the aggregate cells were mixed with the microspheres. They also included a fluorescent dye in the microspheres so the degree of incorporation of the microspheres within the embryoid bodies could be assessed using fluorescent microscopy and spectroscopy.\n\u003C\/p\u003E\n\u003Cp\u003EThe results revealed that the microspheres were incorporated into embryoid bodies under a variety of mixing conditions, but that slower rotary speeds and higher microsphere-to-cell ratios resulted in a greater degree of incorporation.\n\u003C\/p\u003E\n\u003Cp\u003ENext, the researchers compared differentiation of untreated cells, cells mixed with empty microspheres, cells mixed with retinoic acid-loaded microspheres, and cells treated with soluble retinoic acid. Retinoic acid was chosen initially because it is a potent inducer of embryonic stem cell differentiation.\n\u003C\/p\u003E\n\u003Cp\u003EAfter ten days, approximately 90 percent of the embryoid bodies mixed with retinoic acid-loaded microspheres began to display the hollow structure signifying differentiation, compared to 6 percent of the untreated bodies, 10 percent of the bodies coated with soluble retinoic acid, and 30 percent of the bodies mixed with empty microspheres. In addition, thirty percent of the embryoid bodies mixed with retinoic acid-loaded microspheres were completely hollow in the center, compared to nearly zero percent for the other groups.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022These results suggest that if you can control the signaling by presenting molecules locally on the inside of the embryoid body from biodegradable microspheres, you can effectively change the course and synchrony of differentiation,\u0022 said McDevitt.\n\u003C\/p\u003E\n\u003Cp\u003ETo examine the cells in more detail, McDevitt teamed with Georgia Tech School of Biology chair John McDonald and research scientist Nathan Bowen to conduct microarray gene expression studies to determine cell phenotype. \n\u003C\/p\u003E\n\u003Cp\u003EThe results revealed enhanced expression of fibroblast growth factor 5 (FGF-5) - a marker for primitive ectoderm - in the embryoid bodies mixed with retinoic acid-loaded microspheres compared to the other treatment groups after 10 days. The researchers also confirmed increased or inhibited expression of many additional markers.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022The importance of these findings is that we\u0027ve shown that biomaterial-based approaches to regulate stem cell microenvironments can significantly improve differentiation methods,\u0022 said McDevitt. \u0022Our ultimate goal is to improve the efficiency of this differentiation process into specific cell types for cell replacement therapies.\u0022\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E\nGeorgia Institute of Technology\u003Cbr \/\u003E\n75 Fifth Street, N.W., Suite 100\u003Cbr \/\u003E\nAtlanta, Georgia  30308  USA\n\u003C\/strong\u003E\u003C\/p\u003E\n\u003Cp\u003EMedia Relations Contacts: Abby Vogel (404-385-3364); E-mail: (\u003Ca href=\u0022mailto:avogel@gatech.edu\u0022\u003Eavogel@gatech.edu\u003C\/a\u003E) or John Toon (404-894-6986); E-mail: (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E).\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EWriter:\u003C\/strong\u003E Abby Vogel\n\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Biodegradable microspheres distribute molecules to stem cells"}],"field_summary":[{"value":"New research shows that delivering molecules within aggregates of embryonic stem cells via biodegradable microspheres enhances the efficiency and purity of differentiation.","format":"limited_html"}],"field_summary_sentence":[{"value":"Delivering molecules to stem cells improves differentiation"}],"uid":"27206","created_gmt":"2008-04-09 00:00:00","changed_gmt":"2016-10-08 03:03:24","author":"Abby Vogel Robinson","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2008-04-09T00:00:00-04:00","iso_date":"2008-04-09T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"71347":{"id":"71347","type":"image","title":"McDevitt stem cells","body":null,"created":"1449177367","gmt_created":"2015-12-03 21:16:07","changed":"1475894634","gmt_changed":"2016-10-08 02:43:54"},"71348":{"id":"71348","type":"image","title":"Embryoid bodies stained","body":null,"created":"1449177367","gmt_created":"2015-12-03 21:16:07","changed":"1475894634","gmt_changed":"2016-10-08 02:43:54"},"71349":{"id":"71349","type":"image","title":"McDevitt stem cells2","body":null,"created":"1449177367","gmt_created":"2015-12-03 21:16:07","changed":"1475894634","gmt_changed":"2016-10-08 02:43:54"}},"media_ids":["71347","71348","71349"],"related_links":[{"url":"http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=78","title":"Todd McDevitt"},{"url":"http:\/\/www.bme.gatech.edu\/","title":"Wallace H. Coulter Department of Biomedical Engineering"}],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"7448","name":"aggregate"},{"id":"7451","name":"cystic"},{"id":"7444","name":"differentation"},{"id":"7450","name":"ectoderm"},{"id":"7447","name":"embryoid"},{"id":"7443","name":"embryonic"},{"id":"7452","name":"fibroblast"},{"id":"988","name":"fluorescent"},{"id":"7453","name":"growth factor"},{"id":"7445","name":"microscphere"},{"id":"7446","name":"PLGA"},{"id":"1492","name":"Polymer"},{"id":"523","name":"regenerative"},{"id":"7449","name":"retinoic acid"},{"id":"167397","name":"spectroscopy"},{"id":"167413","name":"Stem Cell"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003EAbby Robinson\u003C\/strong\u003E\u003Cbr \/\u003EResearch News and Publications\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=avogel6\u0022\u003EContact Abby Robinson\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404-385-3364\u003C\/strong\u003E","format":"limited_html"}],"email":["abby@innovate.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}