3D Stem Cell Culture Technology to Shift the Paradigm of Regenerative Medicine
< (From left) KAIST Dr. Changjin Seo, Professor Sangyong Jon >
A breakthrough technology has been developed to overcome the limitation where stem cells fail to survive for long periods in the body, even when administered in large quantities. Stem cells are vital for regenerating damaged tissues or recovering injured areas. A KAIST research team has successfully enhanced both the survival rate and therapeutic efficacy of these cells by developing a 3D culture technology that precisely designs the cellular microenvironment. This achievement is expected to transcend the current limits of stem cell therapy and reshape the landscape of regenerative medicine.
On April 29th, the research team—led by Professor Sangyong Jon from the Department of Biological Sciences and featuring researchers Changjin Seo, Dohyeon Kim, Junhyuk Song, Sun-Young Kim, Youngju Son, and Afia Tasnim Rahman—announced the development of a novel culture technology to grow healthier stem cells. The team implemented a 3D platform by applying a polymer matrix (an artificial structure coating the culture substrate) to an "artificial floor" that mimics the natural in vivo environment. On this platform, they cultured human adipose-derived stem cells (hADSCs) in three dimensions, confirming a dramatic improvement in cellular function and therapeutic impact.
Human adipose-derived stem cells have been favored for clinical use due to their ease of harvest, high proliferation, and low immune rejection. However, traditional 2D (planar) culture methods cause cells to age and lose function over time. Previous 3D methods, such as forming cell aggregates (spheroids), also faced hurdles in maintaining long-term survival and functionality within the body.
To solve this, the research team developed a densely cross-linked synthetic polymer material composed of siloxane (a biocompatible polymer of silicon and oxygen), named "poly-Z."
This material modifies the physicochemical properties of the culture substrate to promote the adsorption of albumin proteins found in the culture medium. As a result, cells do not adhere to the floor but instead self-assemble into 3D spheroid structures. These spheroids showed increased production of the extracellular matrix (ECM), creating an environment highly similar to the human body and demonstrating performance far superior to conventional methods.
Experimental results showed that stem cells cultured on the poly-Z platform exhibited enhanced differentiation potential and immunomodulatory functions, with a significantly increased survival time inside the body.
< Schematic of hADSC Spheroid Formation on the Synthetic Polymer Matrix, Poly-Z >
Notably, in animal models of acute colitis and acute liver injury, this method showed significantly higher therapeutic efficacy than conventional methods. This suggests that even with the same dosage, the cells live longer and act more vigorously. The team confirmed that the activation of integrin and FAK signaling pathways—the mechanisms through which cells sense and respond to their environment—strengthened the stem cells' functions, allowing them to better perceive their surroundings and perform more effectively after transplantation.
Professor Sangyong Jon stated, "This research proves that a precisely engineered synthetic polymer-based 3D environment can simultaneously enhance the function and therapeutic efficacy of stem cells. We expect this to be widely utilized in developing next-generation cell therapies for various incurable diseases, including inflammatory conditions."
The study, with Dr. Changjin Seo from the KAIST InnoCORE AI-Drug Discovery Center as the lead author, was published online on March 31 in the international journal Advanced Science (Impact Factor: 14.1).
Paper Title: Polymer Matrix-Based 3D Culture Significantly Enhances the Differentiation and Immunomodulatory Functions of Human Adipose-Derived Stem Cells
DOI: https://doi.org/10.1002/advs.202518704
This research was supported by the Korea Multi-Ministry Regenerative Medicine Project, the KAIST InnoCORE Program, and the Leader Research Grant of the National Research Foundation of Korea.
Professor Sangyong Jon Appointed Fellow of AIMBE
Professor Sangyong Jon of the Department of Biological Sciences at KAIST has been appointed a member of the American Institute for Medical and Biological Engineering (AIMBE) fellowship.
Established in 1991, AIMBE is a non-profit organization based in Washington, D.C., representing 50,000 individuals and the top 2% of medical and biological engineers. AIMBE provides policy advice and advocacy for medical and biological engineering for the benefit of humanity. It has had about 1,500 fellows over the past 25 years. Among the members, only 110 are non-American nationalities.
Following the appointment of Dr. Hae-Bang Lee, the former senior researcher at the Korean Research Institute of Chemical Technology, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, Professor Jon is the third Korean to become an AIMBE fellow. He had an induction ceremony for the appointment of his fellowship at the AIMBE’s Annual Event held on March 15-17, 2015 in Washington, D.C.
An authority on nanomedicine, Professor Jon has developed many original technologies including multi-functional Theranostics nano particles for the diagnosis and treatment of diseases. He received the Most Cited Paper Award from Theranostics, an academic journal specialized in nanomedicine, last February.
Additionally, Professor Jon is a leading researcher in the field of translational medicine, using a multi-disciplinary, highly collaborative, “Bench to Bedside” approach for disease treatment and prevention. He created a biotechnology venture company and transferred research developments to the industry in Korea.