Ipsita Banerjee earned her BChE from Jadavpur University in Calcutta, India. She then received her MS from the Indian Institute of Science in Bangalore, India. She achieved her PhD in Chemical and Biochemical Engineering from Rutgers University, from which she won the University and Bevier Fellowship for Excellence in Graduate Research.
She serves as an Editorial Board Member of the Journal of Stem Cell Research and Therapy – Omics Publishing Group. Dr. Banerjee has been a proposal panel reviewer for the National Science Foundation in the areas of Biomedical Engineering, IGERT pre-proposal review, Biomechanics and Mechanobiology, and Biotechnology, Biochemical and Biomass Engineering. She is a reviewer for the Journal of Biotechnology, the Journal of Integrative Biology, Cellular and Molecular Bioengineering, the Journal of Biological Engineering, and others. Most recently, Dr. Banerjee received the 2009 NIH Director’s New Innovator Award and the 2009 ORAU Ralph E. Powe Junior Faculty Award, and in 2012 she was selected to participate in the NAE Frontiers of Engineering Education Symposium.
Title of Abstract
An emerging area in tissue engineering is the development of three dimensional engineered constructs, organoids, which are comprised of multiple organ-specific cell populations capable of recapitulating an in-vivo organ system’s structure and function in an in-vitro setting. Engineering tissue specific organoids from human pluripotent stem cells (hPSCs) has resulted in successful reproduction of similar organ functionality from renewable cell source for a variety of target organ systems. Such systems have included derivation of intestinal, brain, and renal organ models. Development of organoid systems requires organ-specific parenchyma cell source and a platform for self-organization and lineage specific induction of chosen cell types. Additionally, reproducing the organ-specific functional vasculature during reproduction of the complex organ structure is extremely vital for maintaining nutrient supply and appropriate organ function. This is particularly crucial while engineering pancreatic islet organoids, since a dense fenestrated intra islet vasculature is vital for supporting glucose delivery and insulin response.
We have developed a novel hydrogel which promotes spontaneous aggregation of pre- differentiated hPSC derived pancreatic progenitor cells (hESC-PPs) into a 3D organoid which demonstrated functional insulin production in vitro as well as in vivo mouse model. The resulting spheroids are readily recoverable and amenable for size and cellular composition tuning. This hydrogel mediated aggregation allowed direct integration of isolated microvessel fragments within the hESC-PP organoids. Continued culture of the multicellular islet organoids promoted microvascular expansion and formation of vascular networks, especially with inclusion of supporting stromal cell populations. Pancreatic phenotype of the vascularized organoids was strengthened, demonstrated by the gene expression of key pancreatic maturation markers (NKX6.1, PDX1, and INS). Moreover, the intra-organoid vasculature demonstrated an increase in islet endothelial specific API gene expression and PLVAP, an indicator of increased endothelial diaphragm and fenestration, key elements of islet vascular development. Implantation of the vascularized organoids under mouse kidney capsules showed resulted in rapid engraftment of the organoids and inosculation with host vasculature, as confirmed with dextran infusion. Both microfragment derived vessels (GFP positive) and host vessels could be detected in the implanted organoids. In conclusion, we believe the results present a major step in the in-vitro production of microvascularized hPSC islet organoids, likely to enhance function and foster faster in-vivo integration, while also being conducive for organ-on-a-chip applications.
Cell-substrate interaction; nanotoxicity evaluation; inflammation modeling; metamodeling of inflammation; decellularized pancreatic matrix for stem cell therapy.
Joseph Candiello (1); Taraka Sai Pavan Grandhi (6); Jacob Dale (8,9); Suzanne bertera (10); Jason Beare (8,9); Kaushal Rege (6,7); Jay Hoying (8,9); Prashant N. Kumta (1,2,3,4,5); Ipsita Banerjee (2,1,5)
All Author Affiliations
Department of BioEngineering, University of Pittsburgh (1); Department of Chemical Engineering, University of Pittsburgh (2); Department of Mechanical Engineering and Material Science, University of Pittsburgh (3); Center for Complex Engineered Multifunctional Materials, University of Pittsburgh (4); McGowan Institute for Regenerative Medicine, University of Pittsburgh (5); Biomedical Engineering, Arizona State University (6); Chemical Engineering, Arizona State University (7); Cardiovascular Innovation Institute, University of Louisville (8); Department of Physiology, University of Louisville (9); Alleghany Health Network (10)