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Advanced Development and Validation of 3 Dimensional Spheroid Culture of Primary Cancer Cells using Nano3D Technology

使用 Nano3D 技术对原发性癌细胞的 3 维球体培养进行高级开发和验证

基本信息

批准号：
9902958
负责人：
Timothy Patrick Spicer
金额：
$ 9.5万
依托单位：
SCRIPPS FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902958
关键词：
3-Dimensional Address Adopted Advanced Development Animal Model Antineoplastic Agents Automation Basic Cancer Research Biological Assay Biological Sciences Biomedical Research Biopsy Cancer Biology Cancer Model Cancer Patient Cancer cell line Cell Culture Techniques Cell Line Cell Proliferation Cell model Cell-Mediated Cytolysis Cells Cellular Spheroids Clinical Clinical Research Clinical Trials Collaborations Collection Communities Complex Consumption Cost efficiency Cytotoxic agent Data Detection Dimensions Disease Doctor of Philosophy Drops Drug Screening Environment Equipment Exposure to FDA approved Force of Gravity Geometry Glioblastoma Goals Gold Growth Heterogeneity Human Image In Vitro Industry KRAS2 gene Laboratories Libraries Literature Magnetism Malignant Neoplasms Malignant neoplasm of pancreas Medicine Methods Modeling Molecular Nanosphere Organoids Pancreas Patients Pharmaceutical Preparations Pre-Clinical Model Primary Neoplasm Production Publishing Readiness Reporting Reproducibility Research Research Institute Speed Technology Testing Therapeutic Time Tissues Translations Transplantation Tumor-Derived Validation Xenograft procedure anticancer research base bioprinting cancer cell cell assembly cell type cost cost effective cost effectiveness culture plates density drug discovery drug testing experimental study high throughput screening high throughput technology improved in vitro Model in vitro testing in vivo inhibitor/antagonist innovation iron oxide nanoparticle miniaturize monolayer mutant neoplastic cell new technology novel novel anticancer drug oncology pancreatic cancer cells personalized medicine pre-clinical pre-clinical research precision medicine procedure cost scaffold screening small molecule statistics success tissue culture tumor two-dimensional

项目摘要

PROJECT SUMMARY/ABSTRACT: Two-dimensional (2D) tissue culture models are highly simplified cancer models unable to capture the complexity and heterogeneity found in-vivo. Around 95% of new anticancer drugs eventually fail in clinical trial despite robust indications of activity in existing in vitro pre-clinical models, making in vitro testing some of the least predictive. Three dimensional (3D) spheroid culture models have recently advanced to bridge the “in- vitro to in-vivo gap” and provide the means for assembling more complex cancer relevant tissue microenvironments. Although these 3D models are being adopted by industry and the academic community, they have limitations and are hampered by low throughput, lack of consistency, high costs and the need for clinical validation. The Scripps Research Institute Molecular Screening Center (SRIMSC) in partnership with n3D Biosciences Inc., Greiner Bio-One USA Inc., Dr. Derek Duckett at Scripps Research department of Molecular Therapeutics and Dr. David Tuveson, M.D, Ph.D. at Cold Spring Harbor Laboratory (CSHL), have created a strategic collaboration to advance a novel technology known as 3D magnetic bioprinting. Magnetic 3D bioprinting addresses the these critical issues by utilizing n3D's core technology known as the NanoShuttle to levitate and aggregate cells using magnetic forces to produce spheroids/organoids. The ultimate end product will be an affordable; HTS validated 384 and 1536 microplate format that supports rapid/consistent production of 3D spheroids for a wide array of cell types including primary tumor lines. The end goal is to accelerate 3D spheroid cultivation using screening automation, improve cost efficiency and allow for rapid drug testing such as FDA approved drugs in reformulation/repurposing studies. Advancement of this technology will be facilitated through the following: Aim 1: Validation of the current 384 well plate nanosphere technology in a HTS facility for automation compatibility. Compare 3D results to 2D models of KRAS pancreatic cancer cell models as provided by Dr. Tuveson. Aim 2: Validation of n3D spheroid technology for drug testing against select cytotoxic drugs, NCI approved oncology drug set and the Scripps FDA Approved drug collection. CC50 data, i.e. the concentration that produces 50% cellular cytotoxicity, in 2D and in 3D formats will be compared to published literature. Aim 3: n3D Biosciences will produce an advance 1536 well plate NanoShuttle driver compatible for HTS and drug discovery efforts. SRIMSC will evaluate and implement the higher density format for drug discovery utility which will culminate in its testing on a large library of ~150K compounds to demonstrate HTS readiness. Aim 4: The n3D spheroid technology will be employed against patient derived primary Glioblastoma Multiform (GBM) derived cells with the end goal of evaluating its utility in primary cancer cell research. Aim 5: The n3D spheroid technology will be evaluated in-vivo for pancreatic orthotopic tumor effect and its utility in preclinical research. The end goal is to transfer and implement this technology and methods worldwide for cancer research and early drug discovery.

项目总结/文摘:

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Using bead injection to model dispensing of 3-D multicellular spheroids into microtiter plates.

使用微珠注射模拟将 3-D 多细胞球体分配到微量滴定板中。

DOI：
10.1016/j.talanta.2017.09.022
发表时间：
2018
期刊：
Talanta
影响因子：
6.1
作者：
Singhera,Fakhar;Cooper,Emily;Scampavia,Louis;Spicer,Timothy
通讯作者：
Spicer,Timothy

Advanced Development of Primary Pancreatic Organoid Tumor Models for High-Throughput Phenotypic Drug Screening.

DOI：
10.1177/2472555218766842
发表时间：
2018-07
期刊：
SLAS discovery : advancing life sciences R & D
影响因子：
0
作者：
Hou S;Tiriac H;Sridharan BP;Scampavia L;Madoux F;Seldin J;Souza GR;Watson D;Tuveson D;Spicer TP
通讯作者：
Spicer TP

A Novel 3D Culture System for High-Throughput Hepatoxicity Screening.

用于高通量肝毒性筛查的新型 3D 培养系统。

DOI：
发表时间：
2018
期刊：
BioProcess international
影响因子：
0
作者：
Spicer,TimothyP;Vega,VirnelizFernández;Scampavia,Louis;Willetts,Lynsey;Vessels,Michelle
通讯作者：
Vessels,Michelle