The establishment of bat lung organoid culture models offers new insights for studying bat-derived infectious diseases.
Bats have long been recognized as significant reservoirs for various infectious diseases, including the severe acute respiratory syndrome coronavirus and the Ebola virus. A recent study has aimed to address the limitations of existing research models by establishing bat lung organoids (BLO) from Rousettus leschenaultia. This groundbreaking work opens up new avenues for exploring viral susceptibility and disease mechanisms related to bat-derived pathogens.
The research was conducted at Ueno Zoo, Tokyo, where lung tissues from bats were harvested between October 2019 and March 2020. The primary goal was to develop complementary models capable of recapitulating the unique biology of bat lungs. By doing so, scientists hope to gain insights not only relevant to the bats themselves but also to the emergence of zoonotic viruses affecting human health.
Prior to this study, researchers relied on cellular lines and primary cultures originating from bats. While useful, these methods fall short of fully representing the complex structural and functional characteristics of bat lung tissues. The introduction of organoid technology—a 3D model system derived from stem cells—provides more accurate representations of native tissues.
To generate the BLO, the researchers utilized advanced Dulbecco’s Modified Eagle’s Medium (DMEM) enriched with Liberase TH to facilitate tissue digestion and isolation of lung epithelial cells. The resultant organoids were characterized through microscopy, demonstrating the preserved architecture and biological activity of bat lung epithelium. Notably, these organoids expressed key receptors, such as Angiotensin-converting enzyme 2 (ACE2) and Transmembrane Protease Serine 2 (TMPRSS2), which are relevant for studies involving coronavirus entry and replication.
The findings from the study indicated clear potential for BLO as functional models to assess susceptibility to viral infections, such as SARS-CoV-2. The researchers emphasized the importance of these models not only for studying viral biology but also for testing therapeutic strategies to target such pathogens.
According to the authors of the article, "Collectively, our established bat organoid culture models including this BLO might become promising in vitro biomaterials to study the biology of bat-derived infectious diseases." This assertion highlights the anticipated impact of this research on public health initiatives, especially considering the potential for bat-derived viruses to spill over to human populations.
Further refinements to the BLO methodology could facilitate broader applications, including virus isolation studies and the examination of immune responses to bat-borne viruses. The study evaluated the susceptibility of BLO to Pteropine orthoreovirus (PRV), demonstrating how this new model can yield important insights about viral pathogenicity.
Current findings suggest BLO can be instrumental for future research, particularly concerning respiratory viral infectious diseases. This will help scientists decipher the unique immune responses observed within bat populations, thereby enhancing prediction capabilities for potential future outbreaks.
Overall, the establishment of BLO provides foundational advancements supporting the exploration of bat-derived infectious agents. The model possesses the capability for longitudinal studies of pathogenesis and therapeutic response, which could be pivotal for developing strategies to mitigate future zoonotic threats.