EFFICIENT DIFFERENTIATION, SCALE-UP, AND MATURATION OF IPS DERIVED CARDIOMYOCYTES

IPS 来源的心肌细胞的有效分化、放大和成熟

基本信息

批准号：
10761485
负责人：
Kacey Ronaldson
金额：
$ 27.54万
依托单位：
LINK BIOSYSTEMS INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-05 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10761485
关键词：
3-Dimensional Address Adult Benchmarking Biology Bioreactors Calcium Cardiac Cardiac Myocytes Cause of Death Cell Count Cell Culture Techniques Cell Line Cell Survival Cell Therapy Cells Clinic Clinical Complex Cultured Cells Cyclic GMP Development Devices Disease Dose Electrodes Engineering Engraftment Event Feedback Gases Generations Goals Hand Harvest Heart Diseases Human In Vitro Infrastructure Isoproterenol Laboratories Link Maintenance Manuals Marketing Measurement Medicine Methodology Modeling Nutrient Outcome Output Patients Perfusion Phase Procedures Production Provider Quality Control Reproducibility Research Research Personnel Resources Sampling Small Business Innovation Research Grant Suspensions Techniques Technology Therapeutic Time Tissue Culture Techniques Training Translations Universities Variant Work clinically relevant commercial application cost cost efficient design directed differentiation disorder subtype fetal improved in silico in vitro Model induced pluripotent stem cell induced pluripotent stem cell derived cardiomyocytes manufacture manufacturing process precision medicine scale up shear stress stem cells success tau Proteins translational model user-friendly

项目摘要

Project Summary/Abstract Cell expansion is a critical step for cell therapy, hindered by expensive and complex bioreactor requirements to yield sufficient cell numbers for adequate dosing and requiring expensive regents to enhance functionality for increased clinical success. Similarly, in-vitro models of cardiac disease using induced pluripotent stem cell derived cardiomyocytes (iPS-CM) are of critical importance to understanding cardiac biology and disease in the human setting. However, inefficient differentiations hinder the robust translation of these models from the bench to clinically useful metrics. Similarly, iPS-CMs are inherently immature and represent fetal like phenotoypes more than their adult counterparts of more relevance for clinical utility. Thus, there is a need for the reliable production of iPS-CMs of high quality, yield, and maturity. To address this, Link provides low-shear pumpless perfusion bioreactors contatining organotypic niches for the bulk culture of cells in controllable 3D aggregates for enhanced delivery of nutrients, enhanced efficiency of directed differentiations, and increased viability and yeild due to efficient gas and nutrient exchange. These bioreactors require significantly less media than similar bioreactors and substantially less hand-on culture time than current manual workflows. Our devices are cost efficient and simple to use, democratizing patient modeling and cell therapy for both patients, researchers and providers. The increased efficiency of our developed device enables an increase in the patient pool by improving patient access, availability, and applicability to more disease subtypes.

项目概要/摘要细胞扩增是细胞治疗的关键步骤，但由于昂贵且复杂的生物反应器要求而受到阻碍产生足够的细胞数量以进行足够的剂量，并且需要昂贵的试剂来增强功能提高临床成功率。同样，使用诱导多能干细胞的心脏病体外模型衍生心肌细胞（iPS-CM）对于了解心脏生物学和疾病至关重要人文环境。然而，低效的差异化阻碍了这些模型在实验台上的稳健转化临床上有用的指标。同样，iPS-CM 本质上不成熟，更能代表胎儿的表型比成人同行更具有临床实用性。因此，需要可靠的生产高质量、高产量和成熟度的 iPS-CM。为了解决这个问题，Link 提供了低剪切无泵灌注含有器官型生态位的生物反应器，用于在可控 3D 聚集体中大量培养细胞，以增强营养物质的输送，提高定向分化的效率，并提高活力和产量有效的气体和养分交换。这些生物反应器需要的介质比类似的生物反应器少得多与当前的手动工作流程相比，手动培养时间大大减少。我们的设备具有成本效益，并且使用简单，为患者、研究人员和提供者提供患者建模和细胞治疗的民主化。这我们开发的设备提高了效率，通过改善患者就诊机会来增加患者池，可用性以及对更多疾病亚型的适用性。