Efficient patient-specific cell generation by image-guidance

描述（由申请人提供）：该快速通道提案应用先进的动态图像模式识别（KIPR）技术来预测诱导多能干细胞（iPSC）重编程菌落的分化结果，以显着提高分化协议的产量和鲁棒性。提出的工具的目标是：1)教学：通过机器学习为诱导群体分化结果预测创建分数；2)重编程：通过连续菌落评分监测确定最优重编程收获时间；3)分化：选择重编程收获时预测分值最高的菌落进行分化；4)分化：通过持续监测分化过程中细胞簇的质量控制。该快速通道提案的具体目标是第一阶段：1)扩展SVCell以预测诱导的集落分化结果；2)验证对菌落分化结果的预测可以提高CM分化的产量。第二阶段：1)验证该集成系统的稳健性和高产量，适用于多种人类成纤维细胞输入样本和不同的重编程/分化方案；2)将SVCell与最先进的连续细胞成像和培养系统相结合，创建患者特异性细胞生成系统的原型；3)验证集成系统作为患者特异性细胞生成产品。这个快速通道提案的最终目标是开发和验证一个图像引导的高效患者特异性心肌细胞生成系统。这将通过整合我们现有的SVCell软件来实现，该软件包含先进的KIPR技术和活细胞成像技术，以合成针对iPSC的最先进的细胞命运控制协议。患者特异性细胞生成系统可以通过重新编程患者特异性细胞并将其分化到特定谱系（例如心脏，大脑）来进行疾病诊断和个性化药物测试，从而“个性化”药物。病人特异性细胞生成系统的成功开发可以促进个性化医疗，并在诊断和治疗方面彻底改变医疗保健。

DESCRIPTION (provided by applicant): This fast-track proposal applies advanced kinetic image pattern recognition (KIPR) technologies to predict induced pluripotent stem cell (iPSC) reprogramming colonies' differentiation outcomes for significantly improved yield and robustness of differentiation protocols. The objectives of the proposed tool are 1) Teaching: creation of scores for induced colony differentiation outcome prediction by machine learning; 2) Reprogramming: optimal reprogramming harvest time determination by continuous colony score monitoring; 3) Differentiation: selection of colonies with the highest prediction scores for differentiation at the reprogramming harvest time; 4) Differentiation: cell cluster quality control by continuous monitoring during differentiation. The specific aims of this fast-track proposal are Phase I: 1) Extend SVCell for the prediction of induced colony differentiation outcomes ; 2) Validate that prediction of colony differentiation outcomes can improve the yield of CM differentiation. Phase II: 1) Validate that the integrated system can be taught to be robust and high yielding for a diverse set of human fibroblast input samples and different reprogramming / differentiation protocols; 2) Integrate SVCell with a state-of-the-art continuous cell imaging and culture system to create a prototype patient-specific cell generation system; 3) Validate the integrated system as a patient-specific cell generation product. The ultimate goal of this fast-track proposal is to develop and validate an image-guided efficient patient-specific cardiomyocyte generation system. This will be achieved by integrating our established SVCell software containing advanced KIPR technologies with a live cell imaging technology to synthesize state-of-the-art cell fate control protocols against iPSC. Patient-specific cell generation systems could "personalize" medicine by reprogramming patient-specific cells and directing their differentiation to specific lineages (e.g. heart, brain) for disease diagnosis and personalized drug testing. Successful development of the patient-specific cell generation system of this proposal could catalyze personalized medicine and revolutionize health care in both diagnosis and therapy. PUBLIC HEALTH RELEVANCE: Image-guided efficient patient-specific cell generation systems could "personalize" medicine by reprogramming patient-specific cells and directing their differentiation to specific lineages (e.g. heart, brain) for disease diagnosis and personalized drug testing. This could catalyze personalized medicine and revolutionize health care in both diagnosis and therapy.