EAGER: Bioprinting Personalized Islets

EAGER：生物打印个性化胰岛

基本信息

批准号：
1445387
负责人：
Kaiming Ye
金额：
$ 30万
依托单位：
SUNY at Binghamton
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1445387&HistoricalAwards=false
关键词：
EAGER Bioprinting Personalized Islets

项目摘要

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.

提案：1445387PI：YE，Kaimingtitle：急切：CBET的生物医学工程计划中的急切胰岛生物打印将资助开发新技术，以创建能够为糖尿病潜在治疗的葡萄糖挑战的胰岛素分泌的功能性胰岛细胞的开发。新技术基于从人体皮肤衍生的细胞开始，转化为干细胞（人类诱导的多能干细胞或HIPSC）。这些细胞以及为这些细胞提供线索分化的辅助细胞将使用3D打印机以及适当的聚合物基质打印，以创建功能性的“胰岛样”组织。这项工作将通过先进的生物制造技术有助于产生个性化的工程组织，这些技术有可能用于筛查药物或治疗人类疾病。创建高度有组织的多细胞构建体，包括组织和类器官，将革新组织工程和再生药物。这些实验室生产的高阶组织和器官可用于治疗或作为病理生理研究和药物筛查的疾病模型。该急切的奖励旨在探索从人类诱导的多能干细胞多细胞组件中产生生物学功能性胰岛的可行性，其中包括指导性细胞（例如内皮细胞）通过3D生物涂纸。 PIS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作用。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主动通信对于胰岛细胞分化和成熟至关重要。假设患者特异性胰岛通常可以通过在3D打印多细胞组件中区分HIPSC来生成。提议通过用内皮细胞对HIPSC进行构图，从而产生个性化的胰岛，这些胰岛在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）识别3D打印hipsc的生物材料中所需的多细胞组件和2）表征3D打印多细胞支架中HIPSC的胰腺分化。长期的目标是通过将患者特异性的HIPSC印刷为带有内皮细胞包裹的血管导管的3D脚手架来产生个性化胰岛。