Publication: Next-generation human liver models for antimalarial drug assays
Issued Date
2021-06-01
Resource Type
ISSN
20796382
Other identifier(s)
2-s2.0-85107826275
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antibiotics. Vol.10, No.6 (2021)
Suggested Citation
Kasem Kulkeaw Next-generation human liver models for antimalarial drug assays. Antibiotics. Vol.10, No.6 (2021). doi:10.3390/antibiotics10060642 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76157
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Next-generation human liver models for antimalarial drug assays
Author(s)
Other Contributor(s)
Abstract
Advances in malaria prevention and treatment have significantly reduced the related morbidity and mortality worldwide, however, malaria continues to be a major threat to global public health. Because Plasmodium parasites reside in the liver prior to the appearance of clinical manifestations caused by intraerythrocytic development, the Plasmodium liver stage represents a vulnerable therapeutic target to prevent progression. Currently, a small number of drugs targeting liver-stage parasites are available, but all cause lethal side effects in glucose-6-phosphate dehydrogenase-deficient individuals, emphasizing the necessity for new drug development. Nev-ertheless, a longstanding hurdle to developing new drugs is the availability of appropriate in vitro cultures, the crucial conventional platform for evaluating the efficacy and toxicity of drugs in the preclinical phase. Most current cell culture systems rely primarily on growing immortalized or can-cerous cells in the form of a two-dimensional monolayer, which is not very physiologically relevant to the complex cellular architecture of the human body. Although primary human cells are more relevant to human physiology, they are mainly hindered by batch-to-batch variation, limited supplies, and ethical issues. Advances in stem cell technologies and multidimensional culture have allowed the modelling of human infectious diseases. Here, current in vitro hepatic models and toolboxes for assaying the antimalarial drug activity are summarized. Given the physiological potential of pluripotent and adult stem cells to model liver-stage malaria, the opportunities and challenges in drug development against liver-stage malaria is highlighted, paving the way to assess the efficacy of hepatic plasmodicidal activity.