About this Research Topic
The aim of this collection of articles is to assemble advances in stem cell-based approaches and their application to the study of parasitic diseases. Tropical parasites, including unicellular protozoan organisms and helminths, represent a major public health burden, particularly in tropical regions of the world. The study of these organisms is significantly hampered by the lack of effective in vitro/ ex vivo culture systems that mimic natural conditions and facilitate a thorough understanding of parasite development and host-parasite interactions.
The advent of stem cell technology offers the opportunity to derive the right cell types to culture these parasites. Moreover, stem cell-derived organoids accurately reproduce the particular niche in which the parasites grow, develop, interact with host tissues and reproduce. In addition, particularly for helminths (i.e., multicellular parasites), the identification and characterisation of the parasite’s stem cell system, will be critical to complement our current and future understanding of fundamental biological processes, such as worm maturation, and interaction with the host immune system and microbiota.
Protozoan parasites tend to have complex life cycles involving a variety of tissues, many of which are impossible to obtain or cultured routinely. Furthermore, most of the cells are terminally differentiated and some, like the erythrocyte don’t have a nucleus and therefore cannot be genetically manipulated. This has stimulated the development of stem cell-based approaches to establish parasite culture providing more physiological environments and allowing genetic modification. The versatility of this system is demonstrated by the generation of a wide variety of cell types, including erythrocytes and hepatocytes for malaria studies, cardiomyocytes to understand Chagas disease, and macrophages to follow Leishmania. An unprecedented resource is the development of organoids that can replicate the complex niches and architecture of specific tissues. The derivation of intestinal and lung organoids has been shown very useful for the culture of Cryptosporidium, while brain organoids have been used to examine cerebral malaria and neuronal cyst formation in chronic Toxoplasmosis.
Parasitic worms are complex multicellular organisms, with large genomes and free-living as well as parasitic stages across intricate life cycles that can include several hosts. Reproducing in vitro/ ex vivo the natural conditions where the parasites develop, grow, and interact with the host has become the holy grail of the post-genomic era for helminthology. The use of stem cell-based approaches, including the development of key host-derived cell lines and organoids interacting with developmental stages of these metazoan parasites will facilitate the molecular dissection of events that lead to the infection establishment. A recent study successfully demonstrated the use of novel murine cecum organoids to reveal new specific interactions between the host and the larvae of whipworms. Moreover, deciphering the parasite stem cell biology will shine light into worm development and transitions across the life cycle, and hence facilitate the establishment of in vitro/ex vivo culture systems for whole worms, specific tissues or even parasite-derived cell lines.
Notwithstanding these recent efforts, the versatile stem cell system has not been fully exploited for the study of tropical parasites. This collection aspires, to showcase ongoing applications of stem cell technologies in parasitology as well as to stimulate the development of novel approaches to study parasite biology and interactions with hosts and vectors. These approaches will undoubtedly lead to a better understanding of the mechanisms of invasion and survival within the host as well as the identification of parasite vulnerabilities to be exploited as novel strategies for intervention.
The advent of stem cell technology offers the opportunity to derive the right cell types to culture these parasites. Moreover, stem cell-derived organoids accurately reproduce the particular niche in which the parasites grow, develop, interact with host tissues and reproduce. In addition, particularly for helminths (i.e., multicellular parasites), the identification and characterisation of the parasite’s stem cell system, will be critical to complement our current and future understanding of fundamental biological processes, such as worm maturation, and interaction with the host immune system and microbiota.
Protozoan parasites tend to have complex life cycles involving a variety of tissues, many of which are impossible to obtain or cultured routinely. Furthermore, most of the cells are terminally differentiated and some, like the erythrocyte don’t have a nucleus and therefore cannot be genetically manipulated. This has stimulated the development of stem cell-based approaches to establish parasite culture providing more physiological environments and allowing genetic modification. The versatility of this system is demonstrated by the generation of a wide variety of cell types, including erythrocytes and hepatocytes for malaria studies, cardiomyocytes to understand Chagas disease, and macrophages to follow Leishmania. An unprecedented resource is the development of organoids that can replicate the complex niches and architecture of specific tissues. The derivation of intestinal and lung organoids has been shown very useful for the culture of Cryptosporidium, while brain organoids have been used to examine cerebral malaria and neuronal cyst formation in chronic Toxoplasmosis.
Parasitic worms are complex multicellular organisms, with large genomes and free-living as well as parasitic stages across intricate life cycles that can include several hosts. Reproducing in vitro/ ex vivo the natural conditions where the parasites develop, grow, and interact with the host has become the holy grail of the post-genomic era for helminthology. The use of stem cell-based approaches, including the development of key host-derived cell lines and organoids interacting with developmental stages of these metazoan parasites will facilitate the molecular dissection of events that lead to the infection establishment. A recent study successfully demonstrated the use of novel murine cecum organoids to reveal new specific interactions between the host and the larvae of whipworms. Moreover, deciphering the parasite stem cell biology will shine light into worm development and transitions across the life cycle, and hence facilitate the establishment of in vitro/ex vivo culture systems for whole worms, specific tissues or even parasite-derived cell lines.
Notwithstanding these recent efforts, the versatile stem cell system has not been fully exploited for the study of tropical parasites. This collection aspires, to showcase ongoing applications of stem cell technologies in parasitology as well as to stimulate the development of novel approaches to study parasite biology and interactions with hosts and vectors. These approaches will undoubtedly lead to a better understanding of the mechanisms of invasion and survival within the host as well as the identification of parasite vulnerabilities to be exploited as novel strategies for intervention.
Keywords: Stem cell, parasitic diseases, tropical parasites, organoids, Parasitic worms
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