Fully defined matrices for organoid culture

项目摘要 与标准的二维方法相比，三维细胞培养提供了一个机会 以便在受控的实验室条件下更可靠地复制和模拟体内生理学。类器官培养 特别是，已经被证明在体内复制组织发育、分化和疾病生理学 很多情况下。然而，最近的报告表明，目前的细胞培养底物，包括Matrigel，胶原 和其他重组细胞外基质成分，会触发正常建模的不良表型 利用培养的有机物质实现组织功能。在这里，我们提出了一个协作性的第一阶段计划来扩展该实用程序 InSoma的专利偏序聚合物(POPS)在与Scott的三维有机物培养中的应用 Magness，北卡罗来纳大学教堂山分校的博士，胃肠道建模方面的领先专家 使用三维培养系统的组织。我们的概念验证计划旨在优化POP 用于三维培养的配方，评估它们对有机物活性和增殖的支持，以及 使用转录切除法来确定与其他基质相比，异常表型是否减少，例如 马特里格尔。一旦我们建立了有机化合物培养的流行材料的主要配方，第二阶段计划将 评估来自其他组织类型的有机化合物，包括神经、胰腺和肝脏组织以及潜在的 将持久性有机污染物作为体内组织工程方法的支持矩阵的测试。这些产品类别中的每个 在学术研究、药物筛选和组织工程方面都拥有独特的市场。英索玛有 流行生物材料的强大知识产权，以及三维文化的快速增长 对于活体生理学建模，我们预计该产品将满足生命科学工具的巨大市场需求 与Matrigel等市场领先者相比具有特定优势的行业。

Project Summary Compared to standard two dimensional methods, three dimensional cell culture presents an opportunity to more reliably replicate and model in vivo physiology under controlled laboratory conditions. Organoid culture in particular has been shown to replicate in vivo tissue development, differentiation, and disease physiology in many cases. Recent reports however indicate that current cell culture substrates, including Matrigel, collagen and other recombinant extracellular matrix components, trigger undesirable phenotypes for modeling normal tissue function using cultured organoids. Here, we propose a collaborative Phase I program to expand the utility of inSoma’s proprietary Partially Ordered Polymers (POPs) in three-dimensional organoid culture with Scott Magness, PhD of the University of North Carolina at Chapel Hill, a leading expert in modeling gastrointestinal tissues using three dimensional culture systems. Our proof-of-concept program is intended to optimize POP formulations for three-dimensional culture, evaluate their support of organoid viability and proliferation, and employ transcriptomics to determine if aberrant phenotypes are reduced compared to other matrices, such as Matrigel. Once we establish lead formulations of the POP material for organoid culture, a Phase II program would evaluate organoids from other tissue types, including neural, pancreatic and liver tissues as well as potential testing of POPs as a support matrix for in vivo tissue engineering approaches. Each of these product classes has unique markets in both academic research, pharmaceutical screening and tissue engineering. inSoma has a robust intellectual property estate on POP biomaterials and given the rapid growth of three-dimensional culture for modeling in vivo physiology, we anticipate the product to address a significant market in the life science tools sector with specific advantages over market leaders such as Matrigel.