Multicomponent solutions for the preservation of cell therapy products

用于保存细胞治疗产品的多组分解决方案

基本信息

批准号：
10636645
负责人：
ALLISON HUBEL
金额：
$ 38.6万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-03 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10636645
关键词：
Algorithms Amino Acids Behavior Biological Biomanufacturing Biomedical Engineering Breathing Cardiac Cardiac Myocytes Cell Aggregation Cell Differentiation process Cell Separation Cell Therapy Cells Cellular Metabolic Process Complex Cryopreservation Cryopreserved Cell Data Dimethyl Sulfoxide Evolution Exposure to Freezing Funding Geometry Human Hydrogen Bonding Ice Intervention Investigation Membrane Fluidity Metabolic Methods Microscopy Molecular Nature Organism Pathway interactions Plants Raman Spectrum Analysis Rana Recovery Regenerative Medicine Reporting Role Structure Sugar Alcohols System T-Lymphocyte Temperature Therapeutic Therapeutic Uses Tissue Preservation Water Wood material cell type clinical application cold temperature commercial application environmental stressor experience extracellular improved induced pluripotent stem cell induced pluripotent stem cell derived cardiomyocytes mesenchymal stromal cell metabolomics monolayer novel preservation progenitor response success sugar transcriptome sequencing

项目摘要

Project Abstract A novel, biologically inspired strategy will be used to improve DMSO-free preservation of cardiomyocytes derived from human induced pluripotent stem (hiPS) cells cultured as aggregates. Multicellular systems respond poorly to conventional preservation methods. In the previous funding cycle, a differential evolution algorithm was used to optimize the preservation of cells using combinations of sugars, sugar alcohols and amino acids. This approach mimicked the strategies of plants and other simple organisms that survive environmental stresses. Studies characterizing the behavior of multicomponent osmolyte solutions demonstrated that osmolytes present in these solutions interact with each other to modify the behavior of water during freezing which manifests itself at a molecular level (hydrogen bonding) as well as changes in microstructure. The osmolytes also interact with critical biological structures in the cell to stabilize them. Low temperature Raman spectroscopy studies demonstrated that multicellular systems are sensitive to undercooling (the temperature difference between the freezing temperature and the temperature at which ice forms in the extracellular solution). As we transition from single cells to aggregates, once again, we are looking to nature for inspiration. The wood frog uses combinations of osmolytes, suppressed cell metabolism, and minimizes undercooling as it adapts to freezing conditions in the winter. We are proposing a similar approach to improving preservation of cardiomyocyte aggregates. The studies described in the application characterize the freezing response of iPSC-derived cardiomyocytes at the committed cardiac progenitor stage and when formed into fully differentiated, multicellular cardiac constructs. The influence of undercooling on post thaw recovery of fully differentiated multicellular cardiac constructs will also be determined. The influence of suppressing cell metabolism on post thaw recovery of multicellular constructs will also be quantified. On a fundamental level, these studies will advance our understanding of the freezing behavior of more complex multicellular systems. On an applied level, the proposed investigation has the potential to preservation of cells differentiated from hiPS cells through the use of naturally inspired strategies.

项目摘要一种新型的，具有生物学启发的策略将用于改善心肌细胞的无DMSO保存源自人类诱导的多能茎（臀部）细胞，作为聚集体培养。多细胞系统对常规保存方法的反应不佳。在上一个融资周期中，差异演变使用糖，糖醇和氨基酸。这种方法模仿了生存的植物和其他简单生物的策略环境压力。表征多组分渗透溶液的行为的研究证明这些溶液中存在的渗透压相互作用以修改水的行为在冷冻期间，它以分子水平（氢键）以及变化的变化表现出来微观结构。渗透压还与细胞中关键的生物结构相互作用以稳定它们。低的温度拉曼光谱研究表明，多细胞系统对过冷的（冰点温度与冰的温度之间的温度差在细胞外溶液中形成）。当我们从单个单元过渡到聚集物时，我们再次在寻找向大自然启发灵感。木青蛙使用渗透剂的组合，抑制细胞代谢和在适应冬季的冰冻状况时，最小化底口。我们提出了类似的方法改善心肌细胞骨料的保存。应用中描述的研究表征 IPSC衍生的心肌细胞在致力于心脏祖细胞阶段以及何时的冻结反应形成完全分化的多细胞心脏构建体。冷水对解冻后的影响还将确定完全分化的多细胞心脏构建体的恢复。影响抑制细胞代谢对多细胞构建体的融化恢复也将被量化。在这些研究将提高我们对更复杂的冰冻行为的理解多细胞系统。在应用的水平上，提出的研究有可能保存细胞通过使用自然启发的策略与臀部细胞区分开。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative analysis of cell therapy infusion workflows at clinical sites.

DOI：
10.1016/j.jcyt.2020.12.008
发表时间：
2021-04
期刊：
CYTOTHERAPY
影响因子：
4.5
作者：
Joules, Adam;Connors, Julianne;Johnson, Rachel;Van Orsow, Elizabeth A.;McKenna, David H.;Nikiforow, Sarah;Ritz, Jerome;Gee, Adrian;Hubel, Allison
通讯作者：
Hubel, Allison

Differentiation of Human iPS Cells Into Sensory Neurons Exhibits Developmental Stage-Specific Cryopreservation Challenges.