Kaiming Ye, Ph.D.
Professor and Department Chair
Department of Biomedical Engineering
Thomas J Watson School of Engineering and Applied Science
Binghamton University, State University of New York (SUNY)
3D Differentiation of HPSCs into Islets-like Organoids and Tissue manufacturing
The success in directed differentiation of human pluripotent stem cells (HPSC) including embryonic stem (hES) and induced pluripotent stem (iPS) cells into islet-like cells raises new hopes for cell-based diabetes therapy. This, however, has not yet been possible due to the difficulty in generating fully functional beta cells in vitro. In many cases, cells differentiated from HPSCs are immature, or in other words, are unsuitable for cell replacement therapy. Most islet-like cells derived from HPSCs in vitro fail to function normally in vivo after transplantation in diabetic animal models. On the other hand, the in vivo maturation of pancreatic endoderm progenitors presents significant challenges. Here we report a new study on generating islets-like organoids and maturating hESCs-derived pancreatic β cells within a biomimetic 3D scaffold. We discovered that treating cells with (-)-indolactam V is critical to PDX1 and HNF6 expression divergence at Stage II of the differentiation. The expression of PDX1, not HNF6, in these cells indicated the hESC commitment toward pancreatic endocrine, not exocrine cell lineages. 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 characteristics of pancreatic β cells. 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 these cells. A high level production of C-peptide confirmed the de novo endogenous insulin production in these cells. Insulin-secretory granules were detected in these cells, further alluding their high maturity. Exposing cells to a high concentration of glucose induced a sharp increase in insulin secretion, suggesting that they are more sensitive to a glucose challenging due to their elevated maturity. The augment of this technology to other stem cell differentiations will bring cell replacement therapy one step closer to treating many diseases such as diabetes in more controllable clinical settings. In addition, my vision for advanced biomanufacturing and personalized medicine will also be discussed in the seminar.
Dr. Kaiming Ye is Professor and Department Chair of Biomedical Engineering 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.