High-Throughput Tumor-on-a-Chip Platform to Study Tumor-Stroma Interactions and Drug Pharmacokinetics.
High-Throughput Tumor-on-a-Chip Platform to Study Tumor-Stroma Interactions and Drug Pharmacokinetics.
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DOI：
10.1002/adhm.202000880
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发表时间：
2020-11
影响因子：
10
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Chi CW;Lao YH;Ahmed AHR;Benoy EC;Li C;Dereli-Korkut Z;Fu BM;Leong KW;Wang S
Drug screening in oncology, especially for triple-negative breast cancer (TNBC), has high demand but remains unsatisfactory. Currently available models are either nonrepresentative of the complex tumor microenvironment or only suitable for low throughput screening, resulting in a low-yield success for drug development. To tackle these issues, we developed the L-TumorChip system, a three-layered microfluidic tumor-on-a-chip platform integrating tumor microvasculature and tumor-stromal microenvironment with high throughput screening capability. Its layered and modular design is readily scalable through simple integration of multiple units. We validated L-TumorChip with a TNBC model. Our L-TumorChip system emulated certain tumor-stroma complexities and tumor-endothelium interactions, including TNBC invasion through the leaky microvasculature and angiogenesis. Additionally, with this L-TumorChip, we investigated the influence of different stromal cells, including normal fibroblasts, mesenchymal stem cells and cancer-associated fibroblasts (CAF), on cancer cell growth as well as the stromal effects on drug responses to doxorubicin treatment. The presence of CAF delayed drug pharmacokinetics, while apoptotic responses indicated by caspase-3 activities was higher in coculture with normal fibroblasts. Collectively, our L-TumorChip system represents a translational high-throughput screening toolkit that enables drug screening with a scenario closer to the in vivo conditions. This potential use may therefore facilitate development of new cancer drugs. A microfluidic tumor-on-a-chip with integration of tumor-microvasculature and tumorous-stromal microenvironment offers a more representative model to study the cell interactions within tumor microenvironment and between tumor and endothelium barrier. This platform enables more precise high throughput drug screening and drug pharmacokinetic studies.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
DOI：
10.1073/pnas.0609025103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Galaup, Ariane;Cazes, Aurelie;Germain, Stephane
通讯作者：
Germain, Stephane
影响因子：
13.6
作者：
Carvalho, M. R.;Barata, D.;Habibovic, P.
通讯作者：
Habibovic, P.
影响因子：
4.6
作者：
Cavo M;Fato M;Peñuela L;Beltrame F;Raiteri R;Scaglione S
通讯作者：
Scaglione S
影响因子：
3.7
作者：
Jeong SY;Lee JH;Shin Y;Chung S;Kuh HJ
通讯作者：
Kuh HJ