Nature Communications · 9 authors, 9 centres
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The study establishes a novel platform by transplanting mouse liver spheroids into the anterior chamber of the mouse eye, enabling non-invasive, longitudinal, and high-resolution in vivo imaging of liver cell functions. The transplanted spheroids engraft, become vascularized and innervated, and retain key hepatocyte features, allowing monitoring of processes like bile secretion, lipid uptake, and steatosis.
The researchers developed a platform to transplant mouse liver spheroids into the anterior chamber of the eye (ACE) of mice for longitudinal, non-invasive in vivo imaging at single-cell resolution. The transplanted spheroids engrafted on the iris, became vascularized and innervated, and retained hepatocyte-specific and liver-like features. Using fluorescent probes and spheroids from reporter mice, the platform was used to monitor hepatocyte cell cycle activity, bile secretion, lipoprotein uptake, and lipid accumulation. In a diet-induced hepatosteatosis model, lipid accumulation in intraocular grafts mirrored that in the native liver. The study also demonstrated the engraftment of human liver spheroids in immunodeficient mice when co-cultured with human liver sinusoidal endothelial cells. Limitations include that the ACE-liver spheroids lack portal vein input and complex hepatic lobule architecture, and thus do not represent a full replacement for the endogenous liver. The authors propose the platform as a valuable tool for pre-clinical research in liver physiology, disease progression, and drug testing.
