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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.

项目总结/摘要细胞扩增是细胞治疗的关键步骤，受到昂贵且复杂的生物反应器要求的阻碍，产生足够的细胞数量用于足够的剂量，并且需要昂贵的试剂来增强功能，提高临床成功率。类似地，使用诱导多能干细胞的心脏病体外模型来源的心肌细胞（iPS-CM）对于理解心脏生物学和疾病至关重要。人类的背景然而，效率低下的差异化阻碍了这些模型从实验台的稳健转换临床上有用的指标。类似地，iPS-CM本质上是不成熟的，并且更多地代表胎儿样表型。与成人相比，其临床实用性更强。因此，需要可靠的生产高品质、高产量和高成熟度的iPS-CM。为了解决这个问题，Link提供了低剪切无泵灌注包含器官型小生境的生物反应器，用于在可控的3D聚集体中大量培养细胞，营养物质的输送，定向分化效率的提高，以及由于有效的气体和养分交换。这些生物反应器比类似的生物反应器需要显著更少的培养基并且比当前的手动工作流程实质上更少的动手培养时间。我们的设备具有成本效益，简单易用，为患者、研究人员和供应商提供患者建模和细胞治疗的民主化。的我们开发的设备的提高的效率能够通过改善患者访问来增加患者池，可用性和适用性，以更多的疾病亚型。