title: High-Throughput Cancer Cell Sphere Formation for Characterizing the Efficacy of Photo Dynamic Therapy in 3D Cell Cultures.
abstract: Photodynamic therapy (PDT), wherein light sensitive non-toxic agents are locally and selectively activated using light, has emerged as an appealing alternative to traditional cancer chemotherapy. Yet to date, PDT efficacy has been mostly characterized using 2D cultures. Compared to 2D cultures, 3D sphere culture generates unique spatial distributions of nutrients and oxygen for the cells that better mimics the in-vivo conditions. Using a novel polyHEMA (non-adherent polymer) fabrication process, we developed a microfluidic sphere formation platform that can (1) generate 1,024 uniform (size variation <10%) cancer spheres within a 2 cm by 2 cm core area, (2) culture spheres for more than 2 weeks, and (3) allow the retrieval of spheres. Using the presented platform, we have successfully characterized the different responses in 2D and 3D cell culture to PDT. Furthermore, we investigated the treatment resistance effect in cancer cells induced by tumor associated fibroblasts (CAF). Although the CAFs can enhance the resistance to traditional chemotherapy agents, no significant difference in PDT was observed. The preliminary results suggest that the PDT can be an attractive alternative cancer therapy, which is less affected by the therapeutic resistance induced by cancer associated cells.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122.
authors.forename: Xia
authors.initials: X
authors.lastname: Lou
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel, Blvd. Ann Arbor, MI 48109-2099, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ingram
authors.affiliation: 1] Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122 [2] Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel, Blvd. Ann Arbor, MI 48109-2099, USA.
authors.forename: Euisik
authors.initials: E
authors.lastname: Yoon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008027:Light; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use / Q000633:toxicity*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D017319:Photosensitizing Agents; D002945:Cisplatin