文章基本信息

标题：Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
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作者：Matthew Li ; Danika Khong ; Ling-Yee Chin 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：6816
DOI：10.1038/s41598-018-24971-2
语种：English
出版社：Springer Nature
摘要：Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in vitro immunomodulation assays. However, many of these immunomodulation assays are imperfectly designed to accurately recapitulate microenvironment conditions where MSCs act. To increase our understanding of MSC efficacy, we herein conduct a systems level microenvironment approach to define compartmental features that can influence the delivery of MSCs' immunomodulatory effect in vitro in a more quantitative manner than ever before. Using this approach, we notably uncover an improved MSC quantification method with predictive cross-study applicability and unveil the key importance of system volume, time exposure to MSCs, and cross-communication between MSC and T cell populations to realize full therapeutic effect. The application of these compartmental analysis can improve our understanding of MSC mechanism(s) of action and further lead to administration methods that deliver MSCs within a compartment for predictable potency.