EAGER: Bioprinting Personalized Islets

建议：1445387 PI：叶凯明职务：EAGER：生物打印个性化胰岛CBET生物医学工程项目的EAGER奖将资助新技术的开发，用于创造能够分泌胰岛素的功能性胰岛细胞，以应对糖尿病的潜在治疗。 这项新技术的基础是从人类皮肤细胞开始，转化为干细胞（人类诱导多能干细胞或hiPSC）。 这些细胞沿着辅助细胞，辅助细胞为这些细胞的分化提供线索，将使用3D打印机，沿着适当的聚合物基质，以创建功能性“胰岛样”组织。 这项工作将有助于通过先进的生物制造技术生成个性化的工程组织，这些技术可能用于筛选药物或治疗人类疾病。创建高度组织化的多细胞结构，包括组织和类器官，将彻底改变组织工程和再生医学。这些实验室制备的高级组织和器官可用于治疗或作为疾病模型用于病理生理学研究和药物筛选。EAGER奖项旨在探索通过3D生物打印从人类诱导多能干细胞多细胞组装体（包括内皮细胞等指导性细胞）生成生物功能胰岛的可行性。PI先前的工作表明3D环境对hESC（人类胚胎干细胞）胰腺分化和成熟的有益影响。从发育生物学获得的一系列证据表明，血管内皮细胞、导管上皮细胞和胰腺内分泌细胞之间的活跃交流对胰岛细胞的分化和成熟至关重要。假设患者特异性胰岛可以通过在3D打印的多细胞组件内分化hiPSC来定制地生成。提出了通过用内皮细胞图案化hiPSC来产生个性化胰岛，这在3D支架内提供了对hiPSC胰腺分化和成熟至关重要的指导性信号。提出了两个目标：1）鉴定用于将hiPSC 3D打印成期望的多细胞组装体的生物材料，以及2）表征3D打印的多细胞支架中的hiPSC的胰腺分化。长期目标是通过将患者特异性hiPSC打印到具有内皮细胞嵌入的血管导管图案的3D支架中来生成个性化胰岛。

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.