A new chimera protein creates a potent, xeno-free fibrin scaffold with strong cell adhesion, paving the way for reproducible and medically applicable stem cell therapies

Osaka, Japan - Scientists at The University of Osaka have developed a novel hydrogel that enables the efficient, three-dimensional (3D) culture of human induced pluripotent stem cells (iPSCs). By creating a unique fusion protein that combines the properties of fibrin and the cell-adhesion molecule laminin-511, an essential extracellular matrix component that supports pluripotent stem cells in early embryos, the team has engineered a synthetic and safe alternative to conventional materials. This new material opens the way to a chemically defined, clinically applicable 3D scaffold that could replace Matrigel, enabling medically relevant organoids from iPS and other stem cells and ultimately advancing regenerative medicine and drug discovery.

The growing use of organoids in regenerative medicine has created an urgent need for advanced 3D culture substrates. The current standard, Matrigel, is derived from mouse tumors and is unsuitable for clinical use due to its undefined composition and animal origin. Researchers sought a safe, chemically defined alternative. While fibrin gel is a clinically proven biomaterial, it lacks adhesion for stem cells. This study aimed to overcome this by integrating the potent adhesive properties of laminin-511 into a fibrin scaffold.

The research team has engineered a unique 3D culture system to overcome this limitation. They successfully integrated laminin-511, a protein crucial for stem cell adhesion and proliferation, into a fibrin-based gel. Fibrin is a natural, biocompatible protein, making it an ideal scaffold. The study demonstrated that human iPSCs can be successfully grown *within* this specialized gel, allowing them to proliferate in a 3D structure that more closely resembles how cells grow in living tissues. This method is expected to maintain the cells' viability and pluripotency more effectively than conventional techniques.

This innovative culture method could revolutionize the production of stem cells for therapeutic use. As a chemically defined, xeno-free alternative to Matrigel for 3D stem cell culture, it directly addresses key safety and reproducibility concerns. Its stronger cell-adhesive properties also pave the way for generating clinically applicable organoids and advancing regenerative medicine without the limitations of animal-derived materials.
“Our laminin-511 E8 fragment is widely used for 2D culture, but Matrigel still reigns supreme for 3D organoid creation,” says Professor Kiyotoshi Sekiguchi, senior author. “After much trial and error, we arrived at this Chimera-511 protein. The road to a complete, clinically viable replacement for Matrigel is still long, but this work is a significant step in that direction."
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The article, “Laminin-511-functionalized fibrin gel enables in-gel proliferation of human induced pluripotent stem cells,” was published in Matrix Biology at DOI: https://doi.org/10.1016/j.matbio.2025.10.003



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Human iPS cells grown within the laminin-511-functionalized fibrin gel
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