{ "84844-21625176": { "datetime_modified":"20210802T105853", "datetime_start":"20210804T100000", "datetime_end":"20210804T110000", "has_end_time":1, "date_start":"2021-08-04", "date_end":"2021-08-04", "time_start":"10:00:00", "time_end":"11:00:00", "time_zone":"America\/Detroit", "event_title":"BME PhD Defense: Daniel Clough", "occurrence_title":"", "combined_title":"BME PhD Defense: Daniel Clough: Manufacturing and Transplantation of Stem Cell Derived Beta Cells", "event_subtitle":"Manufacturing and Transplantation of Stem Cell Derived Beta Cells", "event_type":"Presentation", "event_type_id":"16", "description":"Type 1 diabetes is caused by the autoimmune destruction of insulin-producing \u03b2-cells, resulting in a chronic metabolic disorder typically treated with exogenous insulin. Even with the aid of advanced insulin pumps and real time feedback systems, blood glucose levels still deviate outside of the range maintained by native islets, which places the individual at risk for vascular complications and life-threatening hypoglycemic events. Cell replacement therapies have demonstrated the capacity to tightly control blood glucose levels. The wide adoption of cell replacement therapy is hindered by limited availability of donor islets, and the lack of effective methods to support the long-term function of these cells within a clinically accessible site. The results presented in this thesis address these limitations: through studying maturation of human pluripotent progenitor cell (hPPC) derived \u03b2 cells within a transplantable biomaterial platform, and evaluating novel approaches to the implantation and support of these cells during their continued maturation in vivo. \r\n\r\nFirst, I present a study that examined delivery of hPPC-derived pancreatic progenitors within microporous PLG scaffolds into the epididymal fat pad, the murine surrogate for the clinically relevant omental pouch. Kidney capsule injection, the site most commonly utilized to test stem cell-derived \u03b2 cell function in murine models, was the comparison condition. We observed that the microporous sca\ufb00olds supported cell engraftment, however the levels of circulating C-peptide were lower when compared to the kidney capsule condition. The sca\ufb00olds were subsequently modi\ufb01ed to provide sustained release of exendin-4, which led to signi\ufb01cantly increased C-peptide production. Image analysis revealed that exendin-4 releasing scaffolds enhanced the proportion of pancreatic progenitors that matured to monohormonal insulin producing cells.\r\n\r\nNext I present my findings from studying how hPPC-derived \u03b2 cells mature and function within three transplantation sites: the i) scaffold delivery into the epididymal fat pad, ii) scaffold delivery into the subcutaneous space, and iii) the kidney capsule injection (control). Additionally, we investigated the impact of blood glucose levels on maturation of the hPPC-derived \u03b2 cells by transplanting mice with pre- or post-engraftment diabetes induction. Hyperglycemia was ameliorated in the cohorts of mice that received scaffolds into the epididymal fat pad, following a period of in vivo maturation. The function of these cells was demonstrated by the reduction in blood glucose levels, healthy increase in weight, therapeutic levels of circulating human insulin, and healthy responses to glucose challenge tests. The function from the epididymal fat pad was superior to the subcutaneous space and was observed to be comparable to the kidney capsule. No differences were observed in graft function between the cohorts whose grafts matured in a diabetic or non-diabetic environment, yet several differences in gene expression were observed.\r\n\r\nMany of the current differentiation protocols culture the cells above a feeder layer in monolayer, or in suspension within a bioreactor. Typically, these protocols require the disruption of the cell niche during key differentiation stages or pre-transplantation handling. Biomaterial scaffolds maintain the integrity of cell-to-cell and cell-to-matrix connections by providing both a space for cell niche development as well as a vehicle for transplantation into the body. Herein, I present results from testing the developmental stage in which progenitors are seeded into the 3D niche, and two differentiation strategies prior to seeding: monolayer and suspension culture. Maturation was characterized via gene expression analysis, glucose stimulated insulin secretion assay, and nondestructive microscopy utilizing a sfGFP-C-peptide cell line that reports C-peptide production and secretion. We observed that seeding clusters during the key transition phase from pancreatic progenitor to pancreatic endocrine enhanced commitment to the final beta cell fate.\r\n\r\nThis work enhances our understanding of hPPC-derived beta cell manufacturing within scaffolds, and delivery to an extrahepatic site to achieve normoglycemic blood glucose levels.\r\n\r\nDate: Wednesday, August 4, 2021\r\nTime: 10:00 AM\r\nZoom: https:\/\/umich.zoom.us\/j\/98009467275\r\nPassword: betacell\r\nChair: Dr. Lonnie Shea", "occurrence_notes":null, "guid":"84844-21625176@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/84844", "building_id":"null", "building_name":"Off Campus Location", "campus_maps_id":"1", "room":"", "location_name":"Virtual", "has_livestream":1, "livestream_type":"zoom", "livetream_require_login":0, "livestream_id":"98009467275", "livestream_password":"betacell", "livestream_link":"https:\/\/umich.zoom.us\/j\/98009467275", "cost":"", "tags":["biomedical","biomedical engineering","Biosciences","bme","engineering","Medicine","Michigan Engineering","Science"], "website":"", "sponsors":[ { "group_name":"Biomedical Engineering", "group_id":"1143", "website":"https:\/\/www.facebook.com\/profile.php?id=100094127215673" } ], "image_url":"https:\/\/events.umich.edu\/media\/attachments\/2021\/08\/event_84844_original-1.png", "styled_images":{ "event_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_thumb\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_large":"https:\/\/events.umich.edu\/media\/cache\/event_large\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_large_2x":"https:\/\/events.umich.edu\/media\/cache\/event_large_2x\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/event_large_lightbox\/media\/attachments\/2021\/08\/event_84844_original-1.png", "group_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb\/media\/attachments\/2021\/08\/event_84844_original-1.png", "group_thumb_square":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb_square\/media\/attachments\/2021\/08\/event_84844_original-1.png", "group_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large\/media\/attachments\/2021\/08\/event_84844_original-1.png", "group_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large_lightbox\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_large_crop":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_crop\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_list":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_list\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_list_2x":"https:\/\/events.umich.edu\/media\/cache\/event_list_2x\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_grid":"https:\/\/events.umich.edu\/media\/cache\/event_grid\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_grid_2x":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_grid_2x\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_feature_large":"https:\/\/events.umich.edu\/media\/cache\/event_feature_large\/media\/attachments\/2021\/08\/event_84844_original-1.png", "event_feature_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_thumb\/media\/attachments\/2021\/08\/event_84844_original-1.png" }, "occurrence_count":1, "first_occurrence":21625176 } , "84782-21624949": { "datetime_modified":"20210727T181519", "datetime_start":"20210804T100000", "datetime_end":"20210804T110000", "has_end_time":1, "date_start":"2021-08-04", "date_end":"2021-08-04", "time_start":"10:00:00", "time_end":"11:00:00", "time_zone":"America\/Detroit", "event_title":"Rackham Resources and Emergency Funding", "occurrence_title":"", "combined_title":"Rackham Resources and Emergency Funding", "event_subtitle":"", "event_type":"Livestream \/ Virtual", "event_type_id":"24", "description":"During this session you will learn about the resources available to you through Rackham such as conflict resolution services and the Rackham Emergency Fund.\nRegistration is required at https:\/\/myumi.ch\/qgMOW.\nWe want to ensure full and equitable participation in our events. If an accommodation would promote your full participation in this event, please follow the registration link to indicate your accommodation requirements. Please let us know as soon as possible in order to have adequate time, preferably one week, to arrange for your requested accommodations or an effective alternative.", "occurrence_notes":null, "guid":"84782-21624949@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/84782", "building_id":"null", "building_name":"Off Campus Location", "campus_maps_id":"1", "room":"", "location_name":"Online", "has_livestream":0, "cost":"", "tags":["Graduate Students"], "website":"https:\/\/rackham.umich.edu\/event\/rackham-resources-and-emergency-funding\/", "sponsors":[ { "group_name":"Rackham Graduate School", "group_id":"1187", "website":"https:\/\/www.facebook.com\/umichgradschool" } ], "image_url":"", "styled_images":{ "event_thumb":"", "event_large":"", "event_large_2x":"", "event_large_lightbox":"", "group_thumb":"", "group_thumb_square":"", "group_large":"", "group_large_lightbox":"", "event_large_crop":"", "event_list":"", "event_list_2x":"", "event_grid":"", "event_grid_2x":"", "event_feature_large":"", "event_feature_thumb":"" }, "occurrence_count":1, "first_occurrence":21624949 } , "84839-21625132": { "datetime_modified":"20210730T181523", "datetime_start":"20210804T104500", "datetime_end":"20210804T130000", "has_end_time":1, "date_start":"2021-08-04", "date_end":"2021-08-04", "time_start":"10:45:00", "time_end":"13:00:00", "time_zone":"America\/Detroit", "event_title":"Summer Research Opportunity Program Research Symposium: Day Two", "occurrence_title":"", "combined_title":"Summer Research Opportunity Program Research Symposium: Day Two", "event_subtitle":"", "event_type":"Livestream \/ Virtual", "event_type_id":"24", "description":"Join our Summer Research Opportunity Program (SROP) scholars as they present their research and answer questions.\nSROP at U-M strives to increase the number of diverse students with unique experiences by supporting their preparation for graduate studies. Through intensive mentorship, active learning, and enrichment activities, SROP fosters a community of scholars who increase social and cultural capital and networking while mastering research skills and knowledge that advance their preparation as candidates for successful graduate study at U-M and success in future careers, increasing representation in professional fields.\nGiven the number of students, presentations will occur over the course of two days\u2014Tuesday, August 3 and Wednesday, August 4. Sixteen scholars will share their research during three rotations beginning at 11:00 a.m., 11:40 a.m., and 12:20 p.m. Guests can join using the main Zoom link and enter into breakout rooms to hear the presentations throughout the three rotations.\n\nGroup Nine\n\nDalissa Negron, Characterizing Selective and Potent Inhibitors of Human DNA Ligase III\nAriane Tsai, Engineering of Microenvironments for Augmented Tendon Healing\n\nGroup Ten\n\nKelotchi Figueroa-Nieves, Theoretical Calculations in Wide Band Gap Materials for Interlayer Exciton\nIsaiah Waters, Continuos and On-Demand Manufacturing of Improved, Personalized Medicines\n\nGroup Eleven\n\nZulma Reyes Benitez, Characterization of Small PAPP-A Inhibitors Blurb: Grew M14 Melanoma Cancer Cell Lines and Measured the Inhibitory Response to Previously Screened Compounds\nKailey Jerome, The Effect of E-Cigarette Vapors on Human Cardiac Tissues\n\nGroup Twelve\n\nCaroline Lindey, Once Ignored, Now Incarcerated: Why China is Pursuing a Policy of Mass Detention of Ethnic Minority Uyghur Muslims in the Xinjiang Uyghur Autonomous Region (XUAR)\nMaimouna Diop, How Colonization Has Impacted West Africans and African Americans Beauty Standards\n\nGroup Thirteen\n\nJose Gonzalez-Rivera, Binge Drinking Behaviors Among Sexual Majority and Minority Youth\nDanielle Amezcua, Religion and Contraceptives in Ann Arbor\n\nGroup Fourteen\n\nLindsey English, Dietary Pesticide Exposure in Mexico City Mothers\nOmar Valdivias Soto, How Parents in Rural Mexico Contextualize Well-Being\n\nGroup Fifteen\n\nVanessa Stubbs, SARS-CoV-2 Variants and Predicted Influences on CD8+ T-cell Responses\nSantiago Garcia-Leco, Understanding Decision Making During Coronavirus in Communities of Color\n\nGroup Sixteen\n\nAila Kassandra Rodriguez, Historical Case Study of Policing, Institutional Changes, and Rise of Black Political Power in Chicago\nKamali Clora, Youth Empowerment Solutions: Engaging Youth for Anti-Racism and Cultural Equity (YES-ERACE) Pilot Implementation\n\nRegistration is required at https:\/\/myumi.ch\/VPEYw.\nWe want to ensure full and equitable participation in our events. If an accommodation would promote your full participation in this event, please follow the registration link to indicate your accommodation requirements. Please let us know as soon as possible in order to have adequate time, preferably one week, to arrange for your requested accommodations or an effective alternative.", "occurrence_notes":null, "guid":"84839-21625132@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/84839", "building_id":"null", "building_name":"Off Campus Location", "campus_maps_id":"1", "room":"", "location_name":"Online", "has_livestream":0, "cost":"", "tags":["Diversity","Graduate Students"], "website":"https:\/\/rackham.umich.edu\/event\/39024\/", "sponsors":[ { "group_name":"Rackham Graduate School", "group_id":"1187", "website":"https:\/\/www.facebook.com\/umichgradschool" } ], "image_url":"", "styled_images":{ "event_thumb":"", "event_large":"", "event_large_2x":"", "event_large_lightbox":"", "group_thumb":"", "group_thumb_square":"", "group_large":"", "group_large_lightbox":"", "event_large_crop":"", "event_list":"", "event_list_2x":"", "event_grid":"", "event_grid_2x":"", "event_feature_large":"", "event_feature_thumb":"" }, "occurrence_count":1, "first_occurrence":21625132 } }