Advancing stem cell regeneration through animal-free culture systems

Intestinal Stem Cells (ISCs) derived from a patient’s own cells have garnered significant attention as a new alternative for treating intractable intestinal diseases due to their low risk of rejection. However, clinical application has been limited by safety and regulatory issues arising from conventional culture methods that rely on animal-derived components (xenogeneic components). A KAIST research team has developed an advanced culture technology that stably grows ISCs without animal components while simultaneously enhancing their migration to damaged tissues and regenerative capabilities.

KAIST announced on December 23^rd that a joint research team—led by Professor Sung Gap Im from the Department of Chemical and Biomolecular Engineering, Dr. Tae Geol Lee from the Nano-Bio Measurement Group at the Korea Research Institute of Standards and Science and Dr. Mi-Young Son from the Stem Cell Convergence Research Center at the Korea Research Institute of Bioscience and Biotechnology has developed a polymer-based culture platform that dramatically improves the migration and regeneration of ISCs in a xenogeneic-free environment.

To overcome obstacles in the clinical application of stem cell therapies—such as the risk of virus transmission to patients when using substances derived from mouse fibroblasts or Matrigel—the joint research team developed “PLUS” (Polymer-coated Ultra-stable Surface). This polymer-based culture surface technology functions effectively without any animal-derived materials.

PLUS is a synthetic polymer surface coated via a vapor deposition method. By precisely controlling surface energy and chemical composition, it significantly enhances the adhesion and mass-culture efficiency of ISCs. Notably, it maintains identical culture performance even after being stored at room temperature for three years, securing industrial scalability and storage convenience for stem cell therapeutics.

Through proteomics analysis, the research team identified that the expression of proteins related to cytoskeletal reorganization significantly increased in ISCs cultured on the PLUS environment.

Proteomics Analysis: A method used to simultaneously analyze the types and quantitative changes of all proteins present within a cell or tissue.

Specifically, the team confirmed that increased expression of cytoskeleton-binding and actin-binding proteins leads to a stable restructuring of the internal cellular architecture. This provides the power source for stem cells to move faster and more actively across the substrate.

Real-time observations using holotomography microscopy revealed that ISCs cultured on PLUS exhibited a migration speed approximately twice as fast as those on conventional surfaces. Furthermore, in a damaged tissue model, the cells demonstrated outstanding regenerative performance, repairing more than half of the damage within a single week. This proves that PLUS activates the cytoskeletal activity of stem cells, thereby boosting their practical tissue regeneration capabilities.

The newly developed PLUS culture platform is evaluated as a technology that will significantly enhance the safety, mass production, and clinical feasibility of ISCs derived from human pluripotent stem cells (hPSCs). By elucidating the mechanism that simultaneously strengthens the survival, migration, and regeneration of stem cells in a xenogeneic-free environment, the team has established a foundation to fundamentally resolve safety, regulatory, and productivity issues in stem cell therapy.

This research provides a synthetic culture platform that eliminates the dependence on xenogeneic components—which has hindered the clinical application of stem cell therapies—while maximizing the migration and regenerative capacity of stem cells. It will serve as a catalyst for a paradigm shift in the field of regenerative medicine.”

Professor Sung Gap Im of KAIST

Dr. Seonghyeon Park (KAIST), Sang Yu Sun (KAIST), and Dr. Jin Gyeong Son (KRISS) participated as first authors. The research findings were published online on November 26th in Advanced Materials, the leading academic journal in materials science.

• Paper Title: Tailored Xenogeneic-Free Polymer Surface Promotes Dynamic Migration of Intestinal Stem Cells
• DOI: 10.1002/adma.202513371

This research was conducted with support from the Ministry of Science and ICT, the Ministry of SMEs and Startups, the National Research Foundation of Korea, the National Council of Science and Technology Research, KRISS, KRIBB, and the National NanoFab Center.