Digital Twin–Guided Development of Stem Cell Organoids for Disease Modeling and Tissue Repair

The development of stem cell–derived organoids (adult stem cells & pluripotent stem cells) represents a transformative opportunity for disease modeling, drug discovery, and regenerative medicine. However, current organoid technologies suffer from high variability, limited reproducibility, incomplete maturation, and inefficient translation to clinical applications. These limitations are attributed to the complex, dynamic, and multiscale nature of stem cell differentiation and tissue self-organization, which cannot be fully controlled using conventional trial-and-error experimental approaches.

This project proposes a paradigm shift by introducing a digital twin–guided organoid engineering platform in which each biological organoid is paired with a continuously updated computational replica that predicts developmental trajectories, functional maturation, and therapeutic performance. The digital twin will integrate multimodal data, including transcriptomics, proteomics, imaging-based morphology, biomechanical cues, and culture conditions, to enable predictive modeling and closed-loop optimization of organoid development.

Using artificial intelligence, machine learning, and systems biology approaches, the platform will:

• Predict optimal differentiation and maturation pathways,

• Identify critical control points in stem cell fate decisions.

• Minimize batch-to-batch variability.

• Enable real-time adaptive control of culture conditions, and

• Ensure functional quality and safety of organoids for translational use.

The project will demonstrate the technology in disease-relevant organoid systems and tissue repair models, establishing proof-of-concept for both in vitro disease modeling and in vivo regenerative applications. By combining stem cell biology, bioengineering, AI, and digital twin technologies, this will establish a new generation of intelligent, predictive, and scalable organoid manufacturing pipelines.

Ultimately, this project aims to accelerate the translation of organoid technologies toward clinical-grade regenerative therapies, precision medicine, and advanced disease modeling, while significantly reducing development cost, time, and experimental uncertainty.