Simple Paper-based Liver Cell Model for Drug Screening

Kattika Kaarj; Jennifer Ngo; Christina Loera; Patarajarin Akarapipad; Soohee Cho; Jeong Yeol Yoon

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자료유형: 학술저널

저자정보: Kattika Kaarj (The University of Arizona) Jennifer Ngo (The University of Arizona) Christina Loera (The University of Arizona) Patarajarin Akarapipad (The University of Arizona) Soohee Cho (The University of Arizona) Jeong Yeol Yoon (Univ. of Arizona)

저널정보: 한국바이오칩학회 BioChip Journal BioChip Journal Vol.14 No.2

발행연도: 2020.1

수록면: 218 - 229 (12page)

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Investigation of the potential adverse effects of chemicals and drugs is essential during the drug development process. In vitro cell model systems have been developed over the past years towards such toxicity investigation. 96-well plate is the common platform for screening drug toxicity due to its simplicity. However, this platform only offers 2D cell culture environment and lacks the flow of solutions, which fails to provide the suitable environment for the cells to adequately metabolize the drugs, for the media to replenish, and for the metabolites and wastes to be removed. Microfluidic chips populated with human or animal cells, known as organ-on-achip (OOC), can reconcile many issues of in vitro cell models, such as the lack of extracellular matrix and flow as well as the species difference. However, OOC can be complicated to fabricate and operate. To bridge this gap, we utilized paper as a primary substrate for OOC, considering its fibrous structure that can mimic natural extracellular matrix, as well as a syringe pump and filter that are commonly available in most laboratories. Paper microfluidic model was designed and fabricated by wax printing on nitrocellulose paper, seeded and proliferated with liver cells (primary rat hepatocytes and HepG2 cells), and two paper substrates were stacked together to complete the paper model. To this paper-based liver cell model, the following drugs were added: Phenacetin (pain reliever and fever reducer), Bupropion (antidepressant), Dextromethorphan (antidepressant), and phosphate-buffered saline (PBS) as a control, all under a physiologically relevant flow rate. The combination of these drugs with Fluconazole (antifungal drug) was also investigated. Cell count, cell morphology, protein production, and urea secretion after drug treatment confirmed that the model successfully predicted toxicity within 40 minutes. This simple, paper-based liver cell model provided enhanced and faster cell response to drug toxicity and showed comparable or better behavior than the cells cultured in conventional 2D in vitro models.

#Drug toxicity #Paper microfluidics #Organ-on-a-chip #Rat hepatocyte #HepG2

참고문헌 (32)

참고문헌 신청

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