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Biofabrication of Islet Organoids from Human Pluripotent Stem Cells

Wednesday, November 15, 2017, 12:00 PM

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Kaiming Ye, PhD
Professor of Biomedical Engineering
Binghamton University, State University of New York (SUNY)

Biography

Dr. Kaiming Ye is Professor and Department Chair of Biomedical Engineering and Director of Center of Biomanufacturing for Regenerative Medicine at the Binghamton University (BU), State University of New York (SUNY). He is one of the top most distinguished and accomplished leaders in the field of Medical and Biological Engineering. He is fellow of AIMBE and senior member of IEEE. His scholarly contributions to the field include the development of the concept of advanced biomanufacturing and his leadership role in promoting and growing the field. He co-organized more than 10 workshops, including two WTEC studies: one for global assessment of stem cell science and engineering and the other for global assessment of advanced biomanufacturing to promote and grow the field of advanced biomanufacturing, He is well known for his work in bioprinting and pancreatic organoid development from human pluripotent stem cells. He has invented fluorescent nanosensors for continuous glucose monitoring. His work in advanced biomanufacturing was featured as a cover story of ASEE PRISM journal. His work in glucose sensors was featured in the Pittsburgh Post-Gazette. His research has been continuously supported by NIH, NSF, JDRF, ABI and industries. He has chaired and co-chaired a number of international conferences and has delivered keynote/plenary speech in numerous international and national conferences. He serves as Editor-in-Chief, Executive Editor, Associate Editor, and member of Editorial Boards of 13 journals. He is also a highly accomplished administrator and has contributed significantly to national policy-make in science and engineering. During his tenure at NSF, he directed a biomedical engineering program, making funding decisions and implementing post-award management. He was member of a number of interagency working groups, including the Interagency Workgroup for Neuroscience under the Office of Science and Technology Policy (OSTP), Interagency Modeling and Analysis Workgroup, and Multiagency Tissue Engineering and Regenerative Medicine Workgroup. In addition, he was involved in NSF CIF21 IGRET program, cyber-enabled science and engineering program, NIH/NSF joint program on interface between physics and life science, and NIH/NCI-NSF Physicals and Engineering Sciences in Oncology program. Finally, he is a highly accomplished educator in biomedical engineering. As chair of Biomedical Engineering Department at BU, he led the growth of the Department.

Abstract

Creation of highly organized multicellular constructs, including tissues and organoids, will revolutionize tissue engineering and regenerative medicine. The development of these technologies will enable the production of individualized organs for patient-tailored organ transplantation or individualized tissues for cell-based therapy. These lab-produced high order tissues and organs can serve as disease models for pathophysiological study and drug screening. We have developed an innovative tissue assembly technologies for developing islet organoids from human pluripotent stem cells (HPSCs). We discovered that tissue scaffolding and inspirting are critical to the generation of pancreatic endoderm and the assembly of islet architectures. The organoids formed consisted of pancreatic α, β, , and pancreatic polypeptide (PP) cells. A high level co-expression of PDX1, NKX6.1, and NGN3 in these cells suggests the characteristics of pancreatic β cells. More importantly, most insulin-secreting cells generated did not express glucagon, somatostatin, or PP. The expression of mature β cell marker genes such as Pdx1, Ngn3, Insulin, MafA, and Glut2 was detected in generated islet organoids. A high level expression of C-peptide confirmed the de novo endogenous insulin production in these organoids. Insulin-secretory granules, an indication of β cell maturity, were detected. Glucose challenging experiments suggested that these organoids are sensitive to glucose levels due to their elevated maturity. Exposing the organoids to a high concentration of glucose induced a sharp increase in insulin secretion. Finally, we discovered the intra-islet microvascularization, leading to the development of fully functional islet organoids. Cell and tissue fabrication technologies will also be discussed in this seminar.

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