EAGER: Bioprinting Personalized Islets

EAGER：生物打印个性化胰岛

• 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

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：叶凯明 标题：EAGER：生物打印个性化胰岛 这项来自 CBET 生物医学工程项目的 EAGER 奖将资助新技术的开发，以创建能够分泌胰岛素的功能性胰岛细胞，以应对葡萄糖挑战，从而实现糖尿病的潜在治疗。 这项新技术的基础是从人类皮肤来源的细胞开始，转化为干细胞（人类诱导多能干细胞或 hiPSC）。 这些细胞以及为这些细胞的分化提供线索的辅助细胞将使用 3D 打印机以及适当的聚合物基质进行打印，以创建功能性的“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。这些实验室生产的高阶组织和器官可用于治疗或作为病理生理学研究和药物筛选的疾病模型。该 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件（包括内皮细胞等指导性细胞）生成具有生物功能的胰岛的可行性。 PI 之前的工作表明 3D 环境对 hESC（人类胚胎干细胞）胰腺分化和成熟具有有益影响。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通讯对于胰岛细胞的分化和成熟至关重要。据推测，可以通过在 3D 打印的多细胞组件中分化 hiPSC 来定制生成患者特异性胰岛。建议通过用内皮细胞对 hiPSC 进行图案化来生成个性化胰岛，从而在 3D 支架内提供对 hiPSC 胰腺分化和成熟至关重要的指导信号。提出了两个目标：1）确定用于将 hiPSC 3D 打印成所需多细胞组件的生物材料，2）表征 3D 打印多细胞支架中 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血管导管图案的 3D 支架中来生成个性化胰岛。

项目成果

Decellularized Tissue Matrix Enhances Self-Assembly of Islet Organoids from Pluripotent Stem Cell Differentiation

脱细胞组织基质增强多能干细胞分化产生的胰岛类器官的自组装

• DOI: 10.1021/acsbiomaterials.0c00088
• 发表时间: 2020-07
• 期刊: ACS Biomaterials Science & Engineering
• 影响因子: 5.8
• 作者: Bi, Huanjing;Karanth, Soujanya S.;Ye, Kaiming;Stein, Roland;Jin, Sha
• 通讯作者: Jin, Sha

Proteomic analysis of decellularized pancreatic matrix identifies collagen V as a critical regulator for islet organogenesis from human pluripotent stem cells

脱细胞胰腺基质的蛋白质组学分析确定胶原蛋白 V 是人类多能干细胞胰岛器官发生的关键调节因子

• DOI: 10.1016/j.biomaterials.2019.119673
• 发表时间: 2020-03
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Bi, Huanjing;Ye, Kaiming;Jin, Sha
• 通讯作者: Jin, Sha