In Vitro Immune Organs-on-Chip for Drug Development: A Review
Abstract
:1. Introduction
2. Immune Organs-on-Chip
2.1. Skin-on-Chip
2.2. Gut-on-Chip
2.3. Liver-on-Chip
2.4. Lymph Node-on-Chip
2.5. Spleen-on-Chip
2.6. Bone Marrow-on-Chip
2.7. Lymphatic Vessel-on-Chip
2.8. Other Relevant Immune-on-Chip Platforms
3. Towards an Integrated Immune System on Chip
4. Challenges
Funding
Conflicts of Interest
References
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Organ | Simulated Feature/s | Relevance to Drug development | Reference |
---|---|---|---|
Skin | Barrier Function | The skin is a site of administration of some drugs Skin is an active immune organ that reacts to pathogens and foreign substances including drugs Immune rejection to newly developed drugs can be initiated in skin, thus, models assessing drug-skin immune interaction are desirable | [48,49] |
Vascularization | [39,51,52] | ||
Air-to-liquid interface | [49,50] | ||
Absorption | [39] | ||
Inflammation and Edema | [39] | ||
Immune Competence | [53] | ||
Gut | Epithelial Barrier function | The Gut is a site of administration of some drugs (oral administration) The Gut contains various immune components that react to pathogens and foreign substances including drugs Immune rejection to newly developed drugs can be initiated in gut, thus, models assessing drug-gut immune interaction are desirable | [60] |
Peristalsis motion | [61,65,66] | ||
Microbial interface | [61,66,68] | ||
Substance Transport | [61] | ||
Gut viral infection | [41] | ||
Villi | [61,65,66,67] | ||
Immune Competence | [66] | ||
Liver | Liver sinusoid | The liver has been shown to play key roles in immunity containing the body’s largest population of macrophages (Kupffer cells) Drug toxicity to the liver is the most common cause for the discontinuation of clinical trials on a drug, as well as the most common reason for an approved withdrawal of a drug from the marketplace [89] Thus, interactions between liver immune components and drugs should be assessed | [74,80,86,87] |
Substance Transport | [75,79,80,83,84] | ||
Metabolism | [77,80,84] | ||
Bile Canaliculi | [83] | ||
Secretion of liver specific products (urea and albumin) | [82,84,86] | ||
Hepatocyte-endothelial interface | [74,78,81,87] | ||
Hepatocyte-fibroblast interaction | [82] | ||
Hepatocyte-stellate cell interaction | [85] | ||
Hepatitis B virus Replication | [87] | ||
Drug toxicity testing | [77,80,84] | ||
Lymph node | Chemotaxis | Lymph node is the site of immune coordination in the body Adaptive immune responses against newly developed drugs are initiated in the lymph node thus, lymph node models can be utilized to modulate response of immune cells to drugs | [97,98] |
Immune cell interactions | [93,96] | ||
Response to vaccines and drugs | [99,100] | ||
Spleen | Blood filtration | Spleen filters the blood and removes pathogens and other foreign substances including pharmaceutical drugs Models assessing the cleansing process of the spleen which involves immune components such as macrophages are highly desirable especially for assessing how drugs are eliminated | [103,105] |
Blood cleansing | [105] | ||
Bone Marrow | Hematopoietic Niche Formation | The bone marrow is the site of production of all immune cells as well as the site of selection and maturation of B lymphocytes Models examining the development of lymphocytes within bone marrow and investigating the priming process of B-cells as well as the specific cellular mechanism of recognizing and responding to an antigen can aid in developing drugs that are less toxic to the immune system | [40,110] |
Blood and immune cell production | [109,110] | ||
Responsiveness to drugs | [109,111] | ||
Lymphatic vessels | Microcirculation | Exchange of substances between circulatory and lymphatic system occur through lymphatic vessels therefore, models examining how pharmaceutical drugs leave bloodstream and enter into nearby afferent lymphatics are highly desirable | [42] |
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Shanti, A.; Teo, J.; Stefanini, C. In Vitro Immune Organs-on-Chip for Drug Development: A Review. Pharmaceutics 2018, 10, 278. https://doi.org/10.3390/pharmaceutics10040278
Shanti A, Teo J, Stefanini C. In Vitro Immune Organs-on-Chip for Drug Development: A Review. Pharmaceutics. 2018; 10(4):278. https://doi.org/10.3390/pharmaceutics10040278
Chicago/Turabian StyleShanti, Aya, Jeremy Teo, and Cesare Stefanini. 2018. "In Vitro Immune Organs-on-Chip for Drug Development: A Review" Pharmaceutics 10, no. 4: 278. https://doi.org/10.3390/pharmaceutics10040278