Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases

Abstract

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges

“…In this regard, ex vivo organoid models using surgically resected patient tumors are considered promising alternatives to address existing challenges, such as studying patientspecific developmental stages of HCC, selecting appropriate therapy (chemotherapy or radiotherapy), therapy sensitivity screening, and improving treatment efficiency [49][50][51].…”

“…Organoid technology has received tremendous interest in liver bioengineering to mimic liver-like features and functions for biomedical investigations. Recent advances in organoid research indicate that this technology can be applied to culture and fabricate liver organoids for disease models, cancer research, viral infection models, and translational research [49][50][51]150]. Organoid-based approaches offer alternative mini-liverlike platforms for investigating cancer initiation, development, progression, and therapy response assessment.…”

Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies

“…There are several translational barriers, including regulatory, ethical, and technical challenges, which currently need to be addressed for the translation of organoid technology into clinical applications [ 130 ]. These challenges require a multidisciplinary approach among scientists, clinicians, ethicists, and regulatory agencies to develop standardized protocols, ameliorate culture techniques, and establish clear ethical guidelines.…”

“…Advances in culture techniques and biomaterials hold promise for overcoming these challenges and unlocking the full potential of organoid research. A major limitation is the maintenance of cellular functionality and viability over time due to culture conditions, such as media composition and growth factors; as the volume of organoids increases, so does the demand for nutrients and oxygen [ 130 , 137 ]. At the same time, the accumulation of toxic metabolites causes cell death and necrosis.…”