Academic Journal
3D culture reveals dual role of ICAM-1 in mediating tissue-specific human MSC spheroid formation & enhanced immunomodulation.
| Τίτλος: | 3D culture reveals dual role of ICAM-1 in mediating tissue-specific human MSC spheroid formation & enhanced immunomodulation. |
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| Συγγραφείς: | Wang LT; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University (TMU), Taipei, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, TMU, Taipei, Taiwan., Wang HH; Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan., Doan DTT; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University (TMU), Taipei, Taiwan., Lin YF; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University (TMU), Taipei, Taiwan., Liao CY; Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan., Hsu PJ; Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan., Chang CC; Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan., Yen ML; Department of Obstetrics & Gynecology, National Taiwan University (NTU) Hospital & College of Medicine, NTU, Taipei, Taiwan., Liu KJ; National Institute of Cancer Research, NHRI, Tainan, Taiwan., Sytwu HK; National Institute of Infectious Diseases & Vaccinology, NHRI, Zhunan, Taiwan; Graduate Institute of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan., Yen BL; Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan. Electronic address: blyen@nhri.edu.tw. |
| Πηγή: | Biomaterials [Biomaterials] 2026 Jul; Vol. 330, pp. 123998. Date of Electronic Publication: 2026 Jan 09. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE |
| Imprint Name(s): | Publication: <1995-> : Amsterdam : Elsevier Science Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980- |
| Ιατρικοί όροι (MeSH): | Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Intercellular Adhesion Molecule-1*/immunology , Mesenchymal Stem Cells*/cytology , Mesenchymal Stem Cells*/immunology , Mesenchymal Stem Cells*/metabolism , Spheroids, Cellular*/cytology , Spheroids, Cellular*/immunology , Spheroids, Cellular*/metabolism , Cell Culture Techniques, Three Dimensional*/methods , Immunomodulation*, Placenta/cytology ; Bone Marrow Cells/cytology ; Humans ; Female ; Cell Proliferation ; Pregnancy ; Cells, Cultured ; Cell Adhesion ; Gene Expression Profiling |
| Περίληψη: | Three-dimensional (3D) in vitro culture systems may better mimic in vivo physiological conditions, and are easily accessible methods to improve therapeutic effectiveness of human mesenchymal stem cells (MSCs), which with its many sources appear to harbor clinically relevant functional differences. We therefore investigated the impact and elucidated the mechanism(s) of 3D culture on the immunomodulatory capacity of two commonly used MSC sources, bone marrow (BM) and placental (P). In 3D conditions, PMSCs (PMSC 3D) form larger spheroids than BMMSCs (BMMSC 3D), with whole transcriptome profiling revealing significant enrichment of cell adhesion and immunomodulatory pathways. qPCR and functional validation demonstrated the highest expression of numerous key immunomodulatory factors and strongest capacity to inhibit T cell proliferation with PMSC 3D. Bioinformatics analyses predicted Intercellular Adhesion Molecule 1 (ICAM-1) as crucial for both PMSC 3D spheroid formation and enhanced immunomodulatory capacity, which was validated with flow cytometric analyses and further delineated with single-cell RNA sequencing data. To assess mechanistic involvement, we performed knockdown of ICAM-1 which significantly reduced PMSC 3D spheroid size as well as both in vitro and in vivo immunomodulatory capacity. These findings demonstrate that 3D culture significantly enhances the immunomodulatory potential of PMSCs, and reveal ICAM-1 as having a dual role in spheroid formation as well as modulation of immune responses. Our study also highlights the importance of understanding source-specific differences as well as the profound influence of 3D in vitro systems on MSC functions. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: 3D spheroid; Bone marrow MSCs (BMMSCs); Human mesenchymal stem cells (MSCs); Immunomodulation; Intercellular adhesion molecule-1 (ICAM-1); Placental MSCs (PMSCs); Whole transcriptome profiling |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (ICAM1 protein, human) |
| Entry Date(s): | Date Created: 20260114 Date Completed: 20260626 Latest Revision: 20260626 |
| Update Code: | 20260626 |
| DOI: | 10.1016/j.biomaterials.2026.123998 |
| PMID: | 41534229 |
| Βάση Δεδομένων: | MEDLINE |
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