{"221551":{"#nid":"221551","#data":{"type":"news","title":"Microparticles Create Localized Control of Stem Cell Differentiation; Reduce Growth Factor Use","body":[{"value":"\u003Cp\u003EBefore scientists and engineers can realize the dream of using stem cells to create replacements for worn out organs and battle damaged body parts, they\u2019ll have to develop ways to grow complex three-dimensional structures in large volumes and at costs that won\u2019t bankrupt health care systems.\u003C\/p\u003E\u003Cp\u003EResearchers are now reporting advances in these areas by using gelatin-based microparticles to deliver growth factors to specific areas of embryoid bodies, aggregates of differentiating stem cells. The localized delivery technique provides spatial control of cell differentiation within the cultures, potentially enabling the creation of complex three-dimensional tissues. The local control also dramatically reduces the amount of growth factor required, an important cost consideration for manufacturing stem cells for therapeutic applications.\u003C\/p\u003E\u003Cp\u003EThe microparticle technique, which was demonstrated in pluripotent mouse embryonic cells, also offers better control over the kinetics of cell differentiation by delivering molecules that can either promote or inhibit the process. Based on research sponsored by the National Institutes of Health and the National Science Foundation, the developments were reported online July 1 in the journal \u003Cem\u003EBiomaterials\u003C\/em\u003E and were presented at the 11th Annual International Society for Stem Cell Research meeting held in Boston June 12-15, 2013 .\u003C\/p\u003E\u003Cp\u003E\u201cBy trapping these growth factors within microparticle materials first, we are concentrating the signal they provide to the stem cells,\u201d said Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. \u201cWe can then put the microparticle materials physically inside the multicellular aggregate system that we use for differentiation of the stem cells. We have good evidence that this technique can work, and that we can use it to provide advantages in several different areas.\u201d\u003C\/p\u003E\u003Cp\u003EThe differentiation of stem cells is largely controlled by external cues, including morphogenic growth factors, in the three-dimensional environment that surrounds the cells. Most stem cell researchers currently deliver the growth factors into liquid solutions surrounding the stem cell cultures with a goal of creating homogenous cultures of cells. Delivering the growth factors from microparticles, however, provides better control of the spatial and temporal presentation of the molecules that govern the growth and differentiation of the stem cells, potentially allowing formation of heterogeneous structures formed from different cells.\u003C\/p\u003E\u003Cp\u003EGroups of stem cells stick together as they develop, forming multicellular aggregates that form spheroids as they grow. The researchers took advantage of that by driving microparticles containing growth factor BMP4 or noggin \u2013 which inhibits BMP4 signaling \u2013 into layers of stem cells using centrifugation. When the cell aggregates formed, the microparticles became trapped inside.\u003C\/p\u003E\u003Cp\u003EThe researchers used confocal imaging and flow cytometry to observe the differentiation process and found that growth factors in the microparticles directed the cells toward mesoderm and ectoderm tissues just as they do in solution-based techniques. But because the BMP4 and noggin molecules were directly in contact with the cells, much less growth factor was needed to spur the differentiation \u2013 approximately 12 times less than what would be required by conventional solution-based techniques.\u003C\/p\u003E\u003Cp\u003E\u201cOne of the major advantages, in a practical sense, is that we are using much less growth factor,\u201d said McDevitt, who is also director of the Stem Cell Engineering Center at Georgia Tech. \u201cFrom a bioprocessing standpoint, a lot of the cost involved in making stem cell products is related to the cost of the molecules that must be added to make the stem cells differentiate.\u201d\u003C\/p\u003E\u003Cp\u003EBeyond more focused signaling, the microparticles also provided a localized control not available through any other technique. That allowed the researchers to create spatial differences in the aggregates \u2013 a possible first step toward forming more complex structures with different tissue types such as vasculature and stromal cells.\u003C\/p\u003E\u003Cp\u003E\u201cTo build tissues, we need to be able to take stem cells and use them to make many different cell types which are grouped together in particular spatial patterns,\u201d explained Andres M. Bratt-Leal, the paper\u2019s first author and a former graduate student in McDevitt\u2019s lab. \u201cThis spatial patterning is what gives tissues the ability to perform higher order functions.\u201d\u003C\/p\u003E\u003Cp\u003EAfter creating stem cell aggregates with microparticles containing different growth factors, the researchers observed a hemispherical organization of cells for several days, with the different cells remaining spatially segregated.\u003C\/p\u003E\u003Cp\u003E\u201cWe can see the microparticles had effects on one population that were different from the population that didn\u2019t have the particles,\u201d McDevitt said. \u201cThis may allow us to emulate aspects of how development occurs. We can ask questions about how tissues are naturally patterned. With this material incorporation, we have the ability to better control the environment in which these cells develop.\u201d\u003C\/p\u003E\u003Cp\u003EThe microparticles could also provide better control over the kinetics of cell differentiation. Including different amounts of molecules \u2013 one the growth factor and the other its antagonist \u2013 could vary the rate at which the stem cell differentiation proceeds.\u003C\/p\u003E\u003Cp\u003EWhile the research reported in this paper manipulated pluripotent mouse cells, the researchers have moved ahead in performing similar studies with human stem cells and achieved comparable types of results with the microparticle delivery approaches.\u003C\/p\u003E\u003Cp\u003EThe developments not only help move stem cell technologies closer to the clinic, but also provide a new tool for research.\u003C\/p\u003E\u003Cp\u003E\u201cOur findings will provide a significant new tool for tissue engineering, bioprocessing of stem cells and also for better studying early development processes such as axis formation in embryos,\u201d said Bratt-Leal. \u201cDuring development, particular tissues are formed by gradients of signaling molecules. We can now better mimic these signal gradients using our system.\u201d\u003C\/p\u003E\u003Cp\u003EIn addition to those already mentioned, the research team also included Anh H. Nguyen, Katy A. Hammersmith and Ankur Singh, all associated with Georgia Tech and Emory University when the research was conducted.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis research was supported by the National Institutes of Health (NIH) through award GM088291 and the National Science Foundation (NSF) through award CBET 0651739. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the NIH or NSF.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Andres M. Bratt-Leal, Anh H. Nguyen, Katy A. Hammersmith, Ankur Singh and Todd C. McDevitt, \u201cA Microparticle Approach to Morphogen Delivery within Pluripotent Stem Cell Aggregates,\u201d Biomaterials, 2013). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1016\/j.biomaterials.2013.05.079\u0022 title=\u0022http:\/\/dx.doi.org\/10.1016\/j.biomaterials.2013.05.079\u0022\u003Ehttp:\/\/dx.doi.org\/10.1016\/j.biomaterials.2013.05.079\u003C\/a\u003E\u003Cbr \/\u003E\u003Cbr \/\u003E\u003Cstrong\u003EResearch News\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003E177 North Avenue\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EAtlanta, Georgia\u0026nbsp; 30332-0181\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cbr \/\u003E\u003Cstrong\u003EMedia Relations Contact\u003C\/strong\u003E: John Toon (404-894-6986)(\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBy using gelatin-based microparticles to deliver growth factors, researchers are creating three-dimensional structures from stem cells and reducing the use of growth factors needed to promote differentiation.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers are creating three-dimensional structures from stem cells and reducing the use of growth factors."}],"uid":"27303","created_gmt":"2013-07-09 14:26:47","changed_gmt":"2016-10-08 03:14:30","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2013-07-09T00:00:00-04:00","iso_date":"2013-07-09T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"221521":{"id":"221521","type":"image","title":"Making microparticles","body":null,"created":"1449243516","gmt_created":"2015-12-04 15:38:36","changed":"1475894891","gmt_changed":"2016-10-08 02:48:11","alt":"Making microparticles","file":{"fid":"197276","name":"biomaterials7.jpg","image_path":"\/sites\/default\/files\/images\/biomaterials7_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/biomaterials7_0.jpg","mime":"image\/jpeg","size":6353237,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/biomaterials7_0.jpg?itok=CJzqDjNE"}},"221531":{"id":"221531","type":"image","title":"Analyzing stem cells","body":null,"created":"1449243516","gmt_created":"2015-12-04 15:38:36","changed":"1475894891","gmt_changed":"2016-10-08 02:48:11","alt":"Analyzing stem cells","file":{"fid":"197277","name":"biomaterials8.jpg","image_path":"\/sites\/default\/files\/images\/biomaterials8_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/biomaterials8_0.jpg","mime":"image\/jpeg","size":2245865,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/biomaterials8_0.jpg?itok=zl5wQxRG"}}},"media_ids":["221521","221531"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"14219","name":"Coulter Department of Biomedical Engineering"},{"id":"65091","name":"differentiation"},{"id":"1960","name":"microparticles"},{"id":"167130","name":"Stem Cells"},{"id":"760","name":"Todd McDevitt"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"39471","name":"Materials"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJohn Toon\u003C\/p\u003E\u003Cp\u003EResearch News\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E(404) 894-6986\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}