Primary Human Pancreatic Cancer Cells Cultivation in Microfluidic Hydrogel Microcapsules for Drug Evaluation

Author:

Song Taiyu1ORCID,Zhang Hui2,Luo Zhiqiang2,Shang Luoran13,Zhao Yuanjin124ORCID

Affiliation:

1. Department of Rheumatology and Immunology Institute of Translational Medicine The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210002 China

2. State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China

3. Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics the International Colaboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

4. Chemistry and Biomedicine Innovation Center Nanjing University Nanjing 210023 China

Abstract

AbstractChemotherapy is an essential postoperative treatment for pancreatic cancer, while due to the lack of effective drug evaluation platforms, the therapeutic outcomes are hampered by tumor heterogeneity among individuals. Here, a novel microfluidic encapsulated and integrated primary pancreatic cancer cells platform is proposed for biomimetic tumor 3D cultivation and clinical drug evaluation. These primary cells are encapsulated into hydrogel microcapsules of carboxymethyl cellulose cores and alginate shells based on a microfluidic electrospray technique. Benefiting from the good monodispersity, stability, and precise dimensional controllability of the technology, the encapsulated cells can proliferate rapidly and spontaneously form 3D tumor spheroids with highly uniform size and good cell viability. By integrating these encapsulated tumor spheroids into a microfluidic chip with concentration gradient channels and culture chambers, dynamic and high‐throughput drug evaluation of different chemotherapy regimens could be realized. It is demonstrated that different patient‐derived tumor spheroids show different drug sensitivity on‐chip, which is significantly consistent with the clinical follow‐up study after the operation. The results demonstrate that the microfluidic encapsulated and integrated tumor spheroids platform has great application potential in clinical drug evaluation.

Funder

National Key Research and Development Program of China

Shenzhen Fundamental Research Program

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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