{"204991":{"#nid":"204991","#data":{"type":"news","title":"Adhesive Differences Enable Separation of Stem Cells to Advance Potential Therapies","body":[{"value":"\u003Cp\u003EA new separation process that depends on an easily-distinguished physical difference in adhesive forces among cells could help expand production of stem cells generated through cell reprogramming. By facilitating new research, the separation process could also lead to improvements in the reprogramming technique itself and help scientists model certain disease processes.\u003C\/p\u003E\u003Cp\u003EThe reprogramming technique allows a small percentage of cells \u2013 often taken from the skin or blood \u2013 to become human induced pluripotent stem cells (hiPSCs) capable of producing a wide range of other cell types. Using cells taken from a patient\u2019s own body, the reprogramming technique might one day enable regenerative therapies that could, for example, provide new heart cells for treating cardiovascular disorders or new neurons for treating Alzheimer\u2019s disease or Parkinson\u2019s disease.\u003C\/p\u003E\u003Cp\u003EBut the cell reprogramming technique is inefficient, generating mixtures in which the cells of interest make up just a small percentage of the total volume. Separating out the pluripotent stem cells is now time-consuming and requires a level of skill that could limit use of the technique \u2013 and hold back the potential therapies.\u003C\/p\u003E\u003Cp\u003ETo address the problem, researchers at the Georgia Institute of Technology have demonstrated a tunable process that separates cells according to the degree to which they adhere to a substrate inside a tiny microfluidic device. The adhesion properties of the hiPSCs differ significantly from those of the cells with which they are mixed, allowing the potentially-therapeutic cells to be separated to as much as 99 percent purity.\u003C\/p\u003E\u003Cp\u003EThe high-throughput separation process, which takes less than 10 minutes to perform, does not rely on labeling technologies such as antibodies. Because it allows separation of intact cell colonies, it avoids damaging the cells, allowing a cell survival rate greater than 80 percent. The resulting cells retain normal transcriptional profiles, differentiation potential and karyotype.\u003C\/p\u003E\u003Cp\u003E\u201cThe principle of the separation is based on the physical phenomenon of adhesion strength, which is controlled by the underlying biology,\u201d said \u003Ca href=\u0022http:\/\/www.me.gatech.edu\/faculty\/garcia\u0022\u003EAndr\u00e9s Garc\u00eda\u003C\/a\u003E, the study\u2019s principal investigator and a professor in Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/www.me.gatech.edu\/\u0022\u003EWoodruff School of Mechanical Engineering\u003C\/a\u003E and the \u003Ca href=\u0022http:\/\/www.ibb.gatech.edu\/\u0022\u003EPetit Institute for Bioengineering and Bioscience\u003C\/a\u003E. \u201cThis is a very powerful platform technology because it is easy to implement and easy to scale up.\u201d\u003C\/p\u003E\u003Cp\u003EThe separation process was described April 7 in the advance online publication of the journal \u003Cem\u003ENature Methods\u003C\/em\u003E. The research was supported by the \u003Ca href=\u0022http:\/\/www.nih.gov\/\u0022\u003ENational Institutes of Health\u003C\/a\u003E (NIH) and the \u003Ca href=\u0022http:\/\/www.nsf.gov\/\u0022\u003ENational Science Foundation\u003C\/a\u003E (NSF), supplemented by funds from the American Recovery and Reinvestment Act (ARRA).\u003C\/p\u003E\u003Cp\u003E\u201cThe scientists applied their new understanding of the adhesive properties of human pluripotent stem cells to develop a quick, efficient method for isolating these medically important cells,\u201d said Paula Flicker, of the National Institutes of Health\u2019s \u003Ca href=\u0022http:\/\/www.nigms.nih.gov\/\u0022\u003ENational Institute of General Medical Sciences\u003C\/a\u003E, which partly funded the research. \u201cTheir work represents an innovative conversion of basic biological findings into a strategy with therapeutic potential.\u201d \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EAn improved separation technique is essential for converting the human induced pluripotent stem cells produced by reprogramming into viable therapies, said \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=78\u0022\u003ETodd McDevitt\u003C\/a\u003E, an associate professor in the \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University\u003C\/a\u003E, and director of Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/scec.gatech.edu\/\u0022\u003EStem Cell Engineering Center\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cFor research purposes, depending on labeling reagents for separation is not a major problem,\u201d said McDevitt, one of the paper\u2019s co-authors. \u201cBut when we move into commercialization and manufacturing of cell therapies for humans, we need a technology approach that is unbiased and able to be scaled up.\u201d\u003C\/p\u003E\u003Cp\u003EThe separation technique, called micro stem cell high-efficiency adhesion-based recovery (\u00b5SHEAR), will allow standardization across laboratories, providing consistent results that don\u2019t depend on the skill level of the users.\u0026nbsp; \u201cBecause of the engineering and technology involved, and the characterization work, we now have a technology that is readily transferrable,\u201d McDevitt said.\u003C\/p\u003E\u003Cp\u003EThe \u00b5SHEAR process grew out of an understanding of how cells involved in the reprogramming process change morphologically as the process proceeds. Using a spinning disk device, the researchers tested the adhesive properties of the hiPSCs, the parental somatic cells, partially-reprogrammed cells and reprogrammed cells that had begun differentiating. For each cell type, they measured its \u201cadhesive signature\u201d \u2013 the level of force required to detach the cells from a substrate that had been coated with specific proteins.\u0026nbsp; \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe research team, which included Georgia Tech postdoctoral fellows Ankur Singh and Shalu Suri, tested their technique in microfluidic devices developed in collaboration with \u003Ca href=\u0022http:\/\/www.chbe.gatech.edu\/faculty\/lu\u0022\u003EHang Lu\u003C\/a\u003E, a professor in Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/www.chbe.gatech.edu\/\u0022\u003ESchool of Chemical and Biomolecular Engineering\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003EIn the testing, cells from the culture were first allowed to attach to the substrate before being subjected to the flow of buffer fluid. Cells with a lower adhesive signature detached from the substrate at lower flow rates. By varying the flow rate, the researchers were able to separate specific types of cells, allowing production of stem cell cultures with purity as high as 99 percent \u2013 from mixtures in which those cells accounted for only a few percent of the total.\u003C\/p\u003E\u003Cp\u003E\u201cAt different stages of reprogramming, we see differences in the molecular composition and distribution of the cellular structures that control adhesion force,\u201d Garc\u00eda explained. \u201cOnce we know the range of adhesive forces for each cell type, we can apply those narrow ranges to select the populations that come off in each range.\u201d\u003C\/p\u003E\u003Cp\u003EUsing inexpensive disposable \u201ccassettes,\u201d the microfluidic system could be scaled up to increase the volume of cells produced and to provide specific separations, Garc\u00eda noted.\u003C\/p\u003E\u003Cp\u003EUnlike existing labeling techniques, the new separation process works on cell colonies, avoiding the need to risk damaging cells by breaking up colonies for separation. The separation process has been tested with both reprogrammed blood and skin cells. Cells were provided for testing by ArunA Biomedical, a company based in Athens, Ga., founded by \u003Ca href=\u0022http:\/\/stice.uga.edu\/\u0022\u003EUniversity of Georgia professor Steven Stice\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003EBeyond the direct application in producing stem cells, the separation technique could also help scientists with other research in which cells need to be separated \u2013 including potential improvements in the reprogramming technique, which won the Nobel Prize for medicine in 2012.\u003C\/p\u003E\u003Cp\u003E\u201cCell reprogramming has been a black box,\u201d said McDevitt. \u201cYou start the reprogramming process, and when the cells are fully reprogrammed, you can pick them out visually. But there are really interesting scientific questions about this process, and by isolating cells undergoing reprogramming, we may be able to make new discoveries about how the process occurs.\u201d\u003C\/p\u003E\u003Cp\u003EIn addition to those already mentioned, the project also included graduate student Ted Lee and research technician Marissa Cooke of Georgia Tech, researcher Jamie Chilton of ArunA, and Weiqiang Chen and Jianping Fu of the University of Michigan.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis work was supported by an ARRA supplement to the National Institutes of Health (NIH) awards R01 GM065918 and R43 NS080407, the Stem Cell Engineering Center at Georgia Tech, a Sloan Foundation Fellowship, by the National Science Foundation under award DBI-0649833 and an ARRA sub-award under grant RC1CA144825, and by NSF award CMMI-1129611, the Georgia Tech-Emory Center for Regenerative Medicine (GTEC) and the Parker H. Petit Institute for Bioengineering and Bioscience at Georgia Tech. Any conclusions are those of the authors and do not necessarily represent the official positions of the NIH or NSF.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Singh, Ankur, et al., \u201cAdhesion strength\u2013based, label-free isolation of human pluripotent stem cells,\u201d (Nature Methods, 2013). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1038\/nmeth.2437\u0022\u003Ehttp:\/\/dx.doi.org\/10.1038\/nmeth.2437\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\u0026nbsp; USA\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\u003EA new separation process that depends on an easily-distinguished physical difference in adhesive forces among cells could help expand production of stem cells generated through cell reprogramming. By facilitating new research, the separation process could also lead to improvements in the reprogramming technique itself and help scientists model certain disease processes.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A separation technique based on adhesive force differences could advance stem cell therapies."}],"uid":"27303","created_gmt":"2013-04-07 10:46:47","changed_gmt":"2016-10-08 03:13:59","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2013-04-07T00:00:00-04:00","iso_date":"2013-04-07T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"204931":{"id":"204931","type":"image","title":"Stem cell separation microfluidics1","body":null,"created":"1449179967","gmt_created":"2015-12-03 21:59:27","changed":"1475894861","gmt_changed":"2016-10-08 02:47:41","alt":"Stem cell separation 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