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  3. A three-stage differentiation method for generating induced mesenchymal stem cells from human pluripotent stem cells via gelatin-based screening

A three-stage differentiation method for generating induced mesenchymal stem cells from human pluripotent stem cells via gelatin-based screening

  • Colloids Surf B Biointerfaces. 2026 Mar:259:115324. doi: 10.1016/j.colsurfb.2025.115324.
Linli Wang 1,  Qiang Li 2,  Yuanyuan Li 2,  Luyao Chen 2,  Jianguo Yang 2,  Peizheng Wang 2,  Tiancheng Zhou 3,  Yu Liu 2,  Yuehua Chen 4,  Hong Wang 5
Affiliations

Affiliations

  • 1 Guangdong Engineering Research Center for antibody drugs and immunoassays, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong Province 510632, PR China; Guangzhou Future Homo sapiens Institute of Biomedicine and Health, Guangzhou 510700, PR China; Guangzhou Regenerative Medicine Research Center, Future Homo sapiens Institute of Regenerative Medicine Co. , Ltd, Guangzhou 510700, PR China. Electronic address: [email protected].
  • 2 Guangzhou Future Homo sapiens Institute of Biomedicine and Health, Guangzhou 510700, PR China; Guangzhou Regenerative Medicine Research Center, Future Homo sapiens Institute of Regenerative Medicine Co. , Ltd, Guangzhou 510700, PR China.
  • 3 Research Center for Development and Regeneration , Guangzhou Institutes of Biomedicine and Science, Chinese Academic and Sciences, Guangzhou 510530, China.
  • 4 Guangzhou Future Homo sapiens Institute of Biomedicine and Health, Guangzhou 510700, PR China; Guangzhou Regenerative Medicine Research Center, Future Homo sapiens Institute of Regenerative Medicine Co. , Ltd, Guangzhou 510700, PR China; Guangzhou Santaicreeon Biopharmaceutical Co., Ltd, Guangzhou 510700, PR China. Electronic address: [email protected].
  • 5 Guangdong Engineering Research Center for antibody drugs and immunoassays, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: [email protected].
PMID: 41349379 DOI: 10.1016/j.colsurfb.2025.115324
Abstract

Human pluripotent stem cell (hPSC)-derived induced mesenchymal stem cells (iMSCs) offer advantages over tissue-derived MSCs in their in unlimited expansion, minimal batch-to-batch variation, controllable pathogen status, and large-scale production potential. Yet traditional iMSC differentiation methods face limitations that necessitate a more efficient approach. Based on the classic TGF-β inhibitor (SB431542) induction system, this study established a three-stage iMSC differentiation method: 10-day Laminin-521/Gelatin induction, 11-day screening on 0.1 % gelatin-coated dishes (enriching precursors via differential cell-gelatin adhesion), and 3-5-day amplification. A xeno-free system was established. Flow cytometry, trilineage differentiation, RNA Sequencing, karyotype analysis, and nude mouse tumorigenicity tests validated iMSC quality. This straightforward, cost-effective method (≈￥2000-3000 for 1 ×10⁸ P0 iMSCs) yields high-purity iMSCs with strong proliferation, tissue-derived MSC-like transcriptomes, and enhanced bone repair capacity in a mouse femoral fracture model. It also further implicates the gelatin DGEA motif (which mimics gelatin's effect) as key for iMSC differentiation, addressing classical iMSC industrialization issues and informing clinical translation.

Keywords

Clinical application; Fracture healing; Gelatin; Mesenchymal stem cells; Motif; RNA-sequencing.

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