Development of a DIVI platform for issue resolution in pre-clinical drug development.

 描述（由申请方提供）：药物诱导的血管损伤（DIVI）是临床前动物研究中的常见现象，通常表现为出血、血管内皮和平滑肌细胞坏死、中膜血细胞浸润和炎症。由于几个原因，DIVI的机制还没有得到很好的理解。临床前GLP动物研究中的DIVI结果可能会中断或阻止有前景的药物进入临床。此外，需要在非人灵长类动物中进行GLP安全性研究，以降低较低物种中早期DIVI发现的风险，这是昂贵的。HemoShear，LLC是一家生物技术研究公司，利用专利方法（US 7，811，782）在体外共培养中恢复动物和人类原代细胞的体内生物学。HemoShear血管系统将原代内皮细胞暴露于与原代平滑肌细胞共培养的血管区域特异性血流动力学。在该系统中，血管细胞从非生理“状态”中被拯救，如通过恢复区域特异性体内形态和功能所指示的。重要的是，HemoShear系统中的细胞对接近体内动物或人体暴露水平的药物浓度表现出有效或毒性反应，这通常与标准2D静态细胞培养系统相差1至2个数量级。HemoShear使用已知DIVI化合物的初步数据表明，我们的科学可以在体外和临床前GLP研究之前预测不可预见的DIVI。2014年，HemoShear因其创新的商业化而获得美国小企业管理局颁发的Tibbetts SBIR奖。本SBIR旨在进一步确认HemoShear DIVI平台在临床前药物发现和开发中的常规商业应用和前瞻性决策。

 DESCRIPTION (provided by applicant): Drug-induced vascular injury (DIVI) is a common phenomenon in pre-clinical animal studies and is typically characterized by hemorrhage, vascular endothelial and smooth muscle cell necrosis, medial blood cell infiltration and inflammation. Mechanisms underlying DIVI are not well understood for several reasons. A DIVI result in a preclinical GLP animal study can interrupt or stop the progression of a promising drug to the clinic. In addition, GLP safety studies in non-human primates required to de-risk early DIVI findings in lower species are costly. HemoShear, LLC is a biotechnology research company that utilizes patented methodologies (US 7,811,782) to restore in vivo biology to animal and human primary cells in co-culture in vitro. The HemoShear vascular system exposes primary endothelial cells to vascular region-specific hemodynamics in co-culture with primary smooth muscle cells. In this system, vascular cells are rescued from a non-physiological "state" as indicated by restoration of region-specific in vivo morphology and function. Importantly, cells in the HemoShear system demonstrate an efficacious or toxic response to drugs at concentrations that approximate in vivo animal or human exposure levels, which are often 1 to 2 orders of magnitude different from standard 2D static cell culture systems. HemoShear's preliminary data with known DIVI compounds show that our science can predict unforeseen DIVI in vitro and prior to pre-clinical GLP studies. In 2014, HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation. The purpose of this SBIR is to further validate the HemoShear DIVI platform for routine commercial application and prospective decision-making in pre-clinical drug discovery and development.