The Stem Cell Revolution Revealing Protozoan Parasites’ Secrets and Paving the Way towards Vaccine Development

Abstract

Protozoan infections are leading causes of morbidity and mortality in humans and some of the most important neglected diseases in the world. Despite relentless efforts devoted to vaccine and drug development, adequate tools to treat and prevent most of these diseases are still lacking. One of the greatest hurdles is the lack of understanding of host–parasite interactions. This gap in our knowledge comes from the fact that these parasites have complex life cycles, during which they infect a variety of specific cell types that are difficult to access or model in vitro. Even in those cases when host cells are readily available, these are generally terminally differentiated and difficult or impossible to manipulate genetically, which prevents assessing the role of human factors in these diseases. The advent of stem cell technology has opened exciting new possibilities to advance our knowledge in this field. The capacity to culture Embryonic Stem Cells, derive Induced Pluripotent Stem Cells from people and the development of protocols for differentiation into an ever-increasing variety of cell types and organoids, together with advances in genome editing, represent a huge resource to finally crack the mysteries protozoan parasites hold and unveil novel targets for prevention and treatment.

Novel systems to study vector-pathogen interactions in malaria

“…The advent of stem cells has opened up exciting new applications and opportunities to understand disease mechanisms, recapitulate cellular systems and genetic characteristics (Pance, 2021). Stem cell research boomed in mammalian studies with the capacity to generate induced pluripotent stem (iPS) cell lines and differentiate into specific cell types, making it possible to generate traditional in vitro cell culture of a single cell type or more complex multicellular structures that recapitulate the characteristics of an organ, also called organoids (Figure 2E).…”

“…In this case, stem cell-derived organoids would be much better suited to create an easy manipulable environment simulating the complexity and variety of tissues. Mammalian gut organoids have been recently engineered aiming to harbor and culture unicellular as well as multicellular pathogens (Pance, 2021;Ramıŕez-Flores et al, 2022) and an application to insects has been suggested (Swevers et al, 2021).…”

Transcriptomic analysis of the adaptation to prolonged starvation of the insect-dwelling Trypanosoma cruzi epimastigotes

“…Emerging technologies of tissue and 3D cell culture may overcome some of these issues. Indeed, pharmacological analysis for the prevention and treatment of diseases caused by unicellular parasites is being improved using these methods to model host-parasite interactions ( Pance, 2021 ). In T. cruzi ony a few reports using these methodologies have been described in the literature and are limited to mammalian stages mostly in cardiac tissues ( da Silva Lara et al., 2018 ; Bozzi et al., 2019 ; Sass et al., 2019a ; Sass et al., 2019b ).…”

In Vitro Assessment of Anticoccidials: Methods and Molecules

“…In vivo studies can only provide an overview of the general benefits of a treatment against coccidiosis, but the key processes that make it effective should be studied in vitro, too. In vitro research allows a detailed step-by-step analysis of the mode of action of a treatment, which is essential for pathogens like coccidia, characterized by a multiphasic life cycle, in order to understand the actual target of the molecule [12]. This review aims to summarize the protocols that have been successfully applied so far and the achieved results, and to suggest potential cues to improve research on this field.…”