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disease’s progression (Figure 6). The team developed both cilium-autophagy metabolic axis as a promising target
in vitro and in vivo models using human PSCs genetically for new treatments. The organoid models used in this
engineered to simulate autosomal dominant (ADPKD) and study provide a more accurate reflection of human PKD
autosomal recessive (ARPKD) forms of the disease. These pathology and offer valuable insights into the disease’s
models displayed key PKD characteristics, such as tubular mechanisms, potentially accelerating the development of
injury, abnormal activation of the renin-angiotensin- effective therapies for PKD.
aldosterone system, and spontaneous cyst formation
in vivo. Through single-cell analysis, the researchers 3.3. Organoids with immune function
identified significant metabolic disruptions, particularly in Organoids with immune function represent a major
autophagy, which played a crucial role in cyst development. advancement in biomedical research by incorporating
The study demonstrated that activating autophagy – either immune cells into organoid models to study immune
by overexpressing ATG5 (an autophagy regulator) or by responses in a more realistic and integrated way.
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disrupting primary cilia – could inhibit cyst formation in Traditionally, organoids have focused on mimicking
both ARPKD and ADPKD organoid models. Furthermore, organ structure and function, but by introducing immune
pharmacological activation of autophagy using minoxidil, components such as macrophages, dendritic cells, T
an FDA-approved drug, effectively reduced cyst formation cells, and B cells, these models can now simulate the
in vivo, suggesting its potential as a therapeutic option. complex interactions between the immune system and
This research highlights the complex relationship between various tissues. This innovation enhances the ability
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cilia, autophagy, and metabolism in PKD, positioning the to investigate immune responses in gut-related diseases

Figure 6. The multiple roles of an organoid xenograft model of PKD replicates key pathophysiological features of human PKD. This in vivo model offers
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a more advanced platform for testing potential drugs and validating genetic pathways for therapeutic targeting. Copyright © 2023 Elsevier Inc.
Abbreviations: iPSC: Induced pluripotent stem cell; NSG: NOD.Cg-Prkd cscid IL2rgtm 1Wjl /SzJ; PC: Polycystin; PKD: Polycystic kidney disease.

Volume 1 Issue 2 (2025) 9 doi: 10.36922/OR025040005