Multi-omics elucidation of recombinant collagen‐mediated modulation of mesenchymal stem cell functions

Introduction

Regenerative medicine leverages the potential of mesenchymal stem cells (MSCs) and biomaterials to overcome the limitations of traditional organ transplantation. Collagen, a key extracellular matrix component, is widely used, yet its molecular interactions with MSCs remain insufficiently understood.

Objectives

This study investigates how recombinant collagens modulate MSC behavior and paracrine functions to inform the development of bioactive scaffolds for tissue regeneration.

Methods

Recombinant type I and III collagens were biosynthesized using Pichia pastoris. Multi-omics analyses, including transcriptomics and proteomics, were conducted to evaluate the effects of these collagens on MSC gene expression, secretory profiles, and functional impacts on fibroblasts, endothelial cells, and macrophages.

Results

Recombinant collagens regulated key MSC pathways related to angiogenesis, wound healing, adhesion, cytoskeletal organization, and osteogenesis. Proteomic data further revealed enhanced secretion of cytokines and growth factors that influenced the behavior of surrounding stromal and immune cells.

Conclusion

Recombinant collagen, as a bioactive material, can remodel the functions of mesenchymal stem cells. Specifically, recombinant type I collagen primarily activates the FAK/RHOA/ROCK signaling pathway, while recombinant type III collagen activates the PI3K/Akt signaling pathway; in contrast, bovine-derived type I collagen mainly regulates glycolysis. These findings further support the potential of recombinant collagen in constructing regenerative medicine scaffolds with intelligent regulatory functions.