Next-Generation Human Liver Models for Antimalarial Drug Assays
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 <i>Plasmodium</i> parasites reside in the liver prior to the appearance of clinical mani...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/6/642 |
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| author | Kasem Kulkeaw |
| author_facet | Kasem Kulkeaw |
| author_sort | Kasem Kulkeaw |
| collection | DOAJ |
| description | 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 <i>Plasmodium</i> parasites reside in the liver prior to the appearance of clinical manifestations caused by intraerythrocytic development, the <i>Plasmodium</i> 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. Nevertheless, 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 cancerous 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. |
| first_indexed | 2024-03-10T10:59:21Z |
| format | Article |
| id | doaj.art-496131b300fb45409e5ffd224b266c18 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T10:59:21Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-496131b300fb45409e5ffd224b266c182023-11-21T21:35:53ZengMDPI AGAntibiotics2079-63822021-05-0110664210.3390/antibiotics10060642Next-Generation Human Liver Models for Antimalarial Drug AssaysKasem Kulkeaw0Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandAdvances 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 <i>Plasmodium</i> parasites reside in the liver prior to the appearance of clinical manifestations caused by intraerythrocytic development, the <i>Plasmodium</i> 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. Nevertheless, 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 cancerous 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.https://www.mdpi.com/2079-6382/10/6/642malariaplasmodiumantimalarial drughepatocyteliver/hepatic organoidpluripotent stem cell |
| spellingShingle | Kasem Kulkeaw Next-Generation Human Liver Models for Antimalarial Drug Assays Antibiotics malaria plasmodium antimalarial drug hepatocyte liver/hepatic organoid pluripotent stem cell |
| title | Next-Generation Human Liver Models for Antimalarial Drug Assays |
| title_full | Next-Generation Human Liver Models for Antimalarial Drug Assays |
| title_fullStr | Next-Generation Human Liver Models for Antimalarial Drug Assays |
| title_full_unstemmed | Next-Generation Human Liver Models for Antimalarial Drug Assays |
| title_short | Next-Generation Human Liver Models for Antimalarial Drug Assays |
| title_sort | next generation human liver models for antimalarial drug assays |
| topic | malaria plasmodium antimalarial drug hepatocyte liver/hepatic organoid pluripotent stem cell |
| url | https://www.mdpi.com/2079-6382/10/6/642 |
| work_keys_str_mv | AT kasemkulkeaw nextgenerationhumanlivermodelsforantimalarialdrugassays |