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Abstract A mutualistic co‐evolution exists between the host and its associated microbiota in the human body. Bacteria establish ecological niches in various tissues of the body, locally influencing their physiology and functions, but also contributing to the well‐being of the whole organism through systemic communication with other distant niches (axis). Emerging evidence indicates that when the composition of the microbiota inhabiting the niche changes toward a pathogenic state (dysbiosis) and interactions with the host become unbalanced, diseases may present. In addition, imbalances within a single niche can cause dysbiosis in distant organs. Current research efforts are focused on elucidating the mechanisms leading to dysbiosis, with the goal of restoring tissue homeostasis. In vitro models can provide critical experimental platforms to address this need, by reproducing the niche cyto‐architecture and physiology with high fidelity. This review surveys current in in vitro host–microbiota research strategies and provides a roadmap that can guide the field in further developing physiologically relevant in vitro models of ecological niches, thus enabling investigation of the role of the microbiota in human health and diseases. Lastly, given the Food and Drug Administration Modernization Act 2.0, this review highlights emerging in vitro strategies to support the development and validation of new therapies on the market.
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Engineered In Vitro Models to Improve the Mechanistic Understanding and Treatment of Neglected Tropical Diseases Caused by Protozoan Parasites
Neglected tropical diseases (NTDs), particularly those caused by trypanosomatid protozoa, impose a significant global burden, disproportionately affecting underserved communities in tropical and subtropical regions. Despite their high mortality rates, associated chronic conditions, and rapid spread due to globalization and climate change, NTDs have historically received minimal research investment. Additionally, existing treatments cause severe adverse effects. While animal models have contributed significantly to our understanding of these diseases, they are limited by technical and financial constraints. Current in vitro approaches predominantly focus on single-cell interactions on stiff substrates; thus, failing to capture tissue-level dynamics crucial for understanding host-parasite interactions. In this scoping literature review, we summarize emerging engineering applications to address these challenges by developing more complex in vitro models. We discuss 36 publications that describe novel strategies employing biomaterials, organoids, spheroids, and microfluidic devices to improve the mechanistic understanding of these NTDs. We also describe how these preclinical models are being used as screening platforms in the drug discovery and repurposing pipeline. To better understand the global scope of this research, we also performed a meta-analysis of the geolocation of the authors whose work was included in this review. This analysis uncovers uneven global participation in these efforts to combat NTDs. Ultimately, we draw attention to the need for a multidisciplinary and transnational approach to mitigate the impact of trypanosomatid NTDs and reduce health inequities globally.
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- Award ID(s):
- 2338708
- PAR ID:
- 10571344
- Publisher / Repository:
- Mary Ann Liebert, Inc.
- Date Published:
- Journal Name:
- GEN Biotechnology
- Volume:
- 3
- Issue:
- 4
- ISSN:
- 2768-1572
- Page Range / eLocation ID:
- 228 to 241
- Subject(s) / Keyword(s):
- Neglected tropical diseases tissue engineering disease models protozoa parasites biomaterials microfluidics
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1089/genbio.2024.0020
