Efficient patient-specific cell generation by image-guidance

描述(申请人提供)：这一快速通道方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)重新编程菌落的分化结果，从而显著提高产量和分化方案的稳健性。该工具的目标是：1)教学：通过机器学习为诱导的菌落分化结果预测创建分数；2)重新编程：通过连续的菌落分数监测确定最佳的重新编程收获时间；3)分化：选择在重新编程的收获时间具有最高分化预测分数的菌落；4)分化：通过在分化过程中持续监测来控制细胞团的质量。这个快速通道方案的具体目标是第一阶段：1)扩展SVcell用于预测诱导集落分化结果；2)验证对集落分化结果的预测可以提高CM分化率。第二阶段：1)验证集成系统对于不同的人类成纤维细胞输入样本和不同的重新编程/分化协议是健壮和高产的；2)将SVcell与最先进的连续细胞成像和培养系统集成，以创建针对患者的原型细胞生成系统；3)验证集成系统作为患者特定的细胞生成产品。这一快速通道建议的最终目标是开发和验证一种图像引导的有效的患者特定心肌细胞生成系统。这将通过将我们已建立的包含先进Kipr技术的SVCell软件与活细胞成像技术相结合来实现，以合成针对IPSC的最先进的细胞命运控制协议。针对患者的细胞生成系统可以通过对患者特定的细胞重新编程，并将其分化到特定的谱系(例如心脏、大脑)，以进行疾病诊断和个性化的药物测试，从而使药物“个性化”。这一方案中针对患者的细胞生成系统的成功开发可能会催化个性化医学，并在诊断和治疗方面革新医疗保健。 与公共卫生相关：图像引导的高效患者特定细胞生成系统可以通过对患者特定细胞重新编程并将其分化到特定谱系(例如心脏、大脑)，以进行疾病诊断和个性化药物测试，从而使药物“个性化”。这可能会催生个性化医学，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.