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Review
. 2022 Jan 27:73:167-182.
doi: 10.1146/annurev-med-042320-023055. Epub 2021 Oct 13.

Organoid Models for Infectious Disease

Sarah E Blutt  1   2 , Mary K Estes  1   3
Affiliations
Review

Organoid Models for Infectious Disease

Sarah E Blutt et al. Annu Rev Med. .

Abstract

Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell-derived organoids provide new tools for the study of human infections. Organoid models recapitulate many characteristics of in vivo disease and are providing new insights into human respiratory, gastrointestinal, and neuronal host-microbe interactions. Increasing culture complexity by adding the stroma, interorgan communication, and the microbiome will improve the use of organoids as models for infection. Organoid cultures provide a platform with the capability to improve human health related to infectious diseases.

Keywords: infection; organoid; pathogenesis; stem cell; therapies.

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Figures

Figure 1
Figure 1
Establishment of pluripotent and tissue stem cell–derived organoids. (a) Pluripotent stem cell–derived organoids originate from embryonic stem cells or terminally differentiated cells that are induced or dedifferentiated synthetically to become stem cells. These stem cells are propagated with growth factors and respond to signals that result in the development of ectoderm, mesoderm, and endoderm. Further growth signals direct differentiation into organ-specific cells. In these organoids the mesenchymal component develops along with the epithelium. (b) Tissue stem cell–derived organoids originate from stem cells that reside in mature organs. Upon isolation and ex vivo culture with defined growth factors, the stem cells will divide indefinitely and, upon manipulation of the growth factors, will differentiate into organoids that consist of the epithelial layer of the tissue from which the stem cells were derived. Figure adapted from image created with BioRender.com.
Figure 2
Figure 2
Modes of delivery of infectious organisms to organoid cultures. (a) Pathogens can be delivered to the lumen of an organoid via microinjection. (b) Organoids can be mechanically disrupted into fragments and incubated with pathogens. The fragments reassemble into intact organoids containing the pathogens within the lumen. (c) Organoids can be enzymatically treated, resulting in single cells. These single cells can be plated on plastic or on membranes to form two-dimensional (2D) monolayers that offer easy access to the apical side of the epithelium, which can be used for pathogen encounters. If 2D organoids are plated on Transwell® membranes, they can be exposed to pathogens either apically or basolaterally. (d) Three-dimensional organoids can also be inverted such that the apical side faces outward to interact with pathogens. Figure adapted from image created with BioRender.com.
Figure 3
Figure 3
Key features of organoid cultures that will advance the use of organoids in infectious disease research. Incorporation of immune cells such as macrophages will be critical in establishing the interactions among the pathogen, the epithelium, and the immune system. Incorporation of the microbiome will also be critical. Interorgan communication will allow a more comprehensive view of the body’s response to infectious agents. Figure adapted from image created with BioRender.com.
See this image and copyright information in PMC

References

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RELATED RESOURCES

    1. Bhatia SN, Ingber DE. 2014. Microfluidic organs-on-chips. Nat. Biotechnol 32(8):760–72 - PubMed
    1. Bar-Ephraim YE, Kretzschmar K, Clevers H. 2020. Organoids in immunological research. Nat. Rev. Immunol 20(5):279–93 - PubMed
    1. Brazovskaja A, Treutlein B, Camp JG. 2019. High-throughput single-cell transcriptomics on organoids. Curr. Opin. Biotechnol 55:167–71 - PubMed
    1. May S, Evans S, Parry L. 2017. Organoids, organs-on-chips and other systems, and microbiota. Emerg. Top. Life Sci 1(4):385–400 - PMC - PubMed

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