Humans in a Dish: The Potential of Organoids in Modeling Immunity and Infectious Diseases.

Nino Iakobachvili,Peter J Peters

doi:10.3389/fmicb.2017.02402

Abstract

For many decades, human infectious diseases have been studied in immortalized cell lines, isolated primary cells from blood and a range of animal hosts. This research has been of fundamental importance in advancing our understanding of host and pathogen responses but remains limited by the absence of multicellular context and inherent differences in animal immune systems that result in altered immune responses. Recent developments in stem cell biology have led to the in vitro growth of organoids that faithfully recapitulate a variety of human tissues including lung, intestine and brain amongst many others. Organoids are derived from human stem cells and retain the genomic background, cellular organization and functionality of their tissue of origin. Thus they have been widely used to characterize stem cell development, numerous cancers and genetic diseases. We believe organoid technology can be harnessed to study host–pathogen interactions resulting in a more physiologically relevant model that yields more predictive data of human infectious diseases than current systems. Here, we highlight recent work and discuss the potential of human stem cell-derived organoids in studying infectious diseases and immunity.

Highlights

Lower respiratory infections, cancers, diarrheal diseases and tuberculosis remain among the top 10 causes of death worldwide (WHO, 2017)
The tissue resident macrophages function to clear cell debris, resolve inflammation and modulate immune responses (Davies et al, 2013); antigen-presenting dendritic cells initiate the adaptive immune response and prime the immune system to future attack (Mildner and Jung, 2014); and lastly, circulating monocytes migrate around the body where they can remain as monocytes, differentiate into macrophages in response to stimulatory signals or acquire antigen presenting abilities (Chow et al, 2011)
(1) Purification of peripheral blood mononuclear cells (PBMC’s) from human blood for short term in vitro culture; but in lower numbers, dendritic cells can be purified straight from blood or tissue resident macrophages from certain tissues, e.g., alveolar macrophages from lungs, (2) Immortalized mononuclear phagocyte system (MPS)-like single cell lines of human or animal origin, e.g., the human monocyte-like THP-1 cell line, the murine macrophage-like J774 cell line, (3) Using animal organisms to study aspects of the system, e.g., non-human primates, zebrafish, mice, humanized mice, cell lineage depleted animals and extrapolating results to humans

Summary

Introduction

Cancers (including those caused by infectious agents), diarrheal diseases and tuberculosis remain among the top 10 causes of death worldwide (WHO, 2017). It is key to note that single cell culture and animal models are widely used and have been instrumental in many scientific advancements in fundamental research, drug and vaccine development, infectious, autoimmune and genetic diseases to name a few.

Results

Conclusion