The use of stem cells and organoids for modeling host-microbe interactions in low-biomass tissues.

Stem cells and organoids have emerged as pivotal biological tools for biologically relevant models. Together, these models realistically recapitulate structural and functional elements of the organ, allowing for studies of cellular, molecular, and genetic features that underpin various diseases that are difficult to observe in low-biomass tissues. Stem cells, and more recently organoids, have been applied as regenerative therapies. The emergence of the microbiome as an occupant throughout different body locales requires new approaches to understand the complex cellular interactions with the host tissue at each site. The success of regenerative medicine strategies and therapeutic development is intricately linked to this understanding and management of host-microbe dynamics. Interactions with the host microbiome and infections can both significantly impair tissue regeneration and compromise the function of stem cell-derived therapies. Therefore, a comprehensive understanding of how pathogens and the microbiome interact with stem cells and organoids is relevant for developing safe and effective regenerative medicine interventions. This review explores the evolving landscape of organoid technology, including a discussion on the importance of stem cell studies and considerations for organoid development that are important for use as models to study microbiome interactions. Additionally, this work describes the pivotal role of cell culture models in advancing host-microbe interaction studies in understudied low-biomass organs such as the stomach and reproductive tract. Through this assessment, we aim to shed light on the potential of these models to transform the approach to studying and managing infectious diseases within the context of regenerative medicine.