EAGER: Bioprinting Personalized Islets

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Proposal: 1445387PI: Ye, KaimingTitle: EAGER: Bioprinting Personalized IsletsThis EAGER award from the Biomedical Engineering Program in CBET will fund the development of new technologies for creating functional islet cells capable of secreting insulin in response to a glucose challenge for potential treatment of diabetes. The new technology is based on starting with cells derived from human skin, transformed into stem cells (human induced pluripotent stem cells or hiPSC). These cells along with helper cells that provide cues to these cells for their differentiation will be printed using an 3D printer, along with an appropriate polymer matrix, to create functional "islet-like" tissues. The work will contribute to the generation of personalized engineered tissues through advanced biomanufacturing technologies that could potentially be used to either screen drugs or treat human disease.Creation of highly organized multicellular constructs, including tissues and organoids, will revolutionize tissue engineering and regenerative medicine. These lab-produced high order tissues and organs can be used for therapy or as disease models for pathophysiological study and drug screening. This EAGER award is designed to explore the feasibility of generating biologically functional islets from human induced pluripotent stem cells multicellular assemblies that include instructive cells such as endothelial cells through 3D bioprinting. PIs previous work suggested a beneficial effect of 3D environments on hESCs (human embryonic stem cell) pancreatic differentiation and maturation. A line of evidence acquired from developmental biology suggests that active communication between vascular endothelial cells, duct epithelial cells, and pancreatic endocrine cells is critical to pancreatic islet cell differentiation and maturation. It is hypothesized that patient-specific pancreatic islets can be customly generated by differentiating hiPSCs within 3D printed multicellular assemblies. It is proposed to generate personalized islets by patterning hiPSCs with endothelial cells, which provide instructive signals critical for hiPSC pancreatic differentiation and maturation, within 3D scaffolds. Two objectives are proposed: 1) To identify biomaterials for 3D printing hiPSCs into desired multicellular assemblies and 2) To characterize pancreatic differentiation of hiPSCs in 3D printed multicellular scaffolds. The long-term goal is to generate personalized islets by printing patient-specific hiPSCs into 3D scaffolds patterned with endothelial cell-embedded vascular conduits.