N-cadherin–mimetic 3D hydrogels program pro-regenerative and immunomodulatory states in human adipose-derived mesenchymal stem cells

n-cadherin–mimetic-3d-hydrogels-program-pro-regenerative-and-immunomodulatory-states-in-human-adipose-derived-mesenchymal-stem-cells
N-cadherin–mimetic 3D hydrogels program pro-regenerative and immunomodulatory states in human adipose-derived mesenchymal stem cells

References

  1. Berebichez-Fridman, R. & Montero-Olvera, P. R. Sources and clinical applications of mesenchymal stem cells: State-of-the-art review. Sultan Qaboos Univ. Med. J. 18, e264–e277 (2018).

    Google Scholar 

  2. Ding, D. C., Shyu, W. C. & Lin, S. Z. Mesenchymal stem cells. Cell. Transpl. 20, 5–14 (2011).

    Google Scholar 

  3. Chen, B. et al. Recent advances in the role of mesenchymal stem cells as modulators in autoinflammatory diseases. Front. Immunol. 15, 1525380 (2024).

    Google Scholar 

  4. Schu, S. et al. Immunogenicity of allogeneic mesenchymal stem cells. J. Cell. Mol. Med. 16, 2094–2103 (2012).

    Google Scholar 

  5. Yang, M. C. et al. Tailored environments for directed mesenchymal stromal cell proliferation and differentiation using decellularized extracellular matrices in conjunction with substrate modulus. Acta Biomater. 187, 110–122 (2024).

    Google Scholar 

  6. Scheiber, A. L. et al. Culture condition of bone marrow stromal cells affects quantity and quality of the extracellular vesicles. Int. J. Mol. Sci. 23, 1017 (2022).

  7. Kusuma, G. D. et al. Effect of 2D and 3D culture microenvironments on mesenchymal stem cell-derived extracellular vesicles potencies. Front. Cell. Dev. Biol. 10, 819726 (2022).

    Google Scholar 

  8. Baruffaldi, D., Palmara, G., Pirri, C. & Frascella, F. 3D cell culture: recent development in materials with tunable stiffness. ACS Appl. Bio Mater. 4, 2233–2250 (2021).

    Google Scholar 

  9. Edmondson, R., Broglie, J. J., Adcock, A. F. & Yang, L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay. Drug Dev. Technol. 12, 207–218 (2014).

    Google Scholar 

  10. Elsayed, M. & Merkel, O. M. Nanoimprinting of topographical and 3D cell culture scaffolds. Nanomedicine 9, 349–366 (2014).

    Google Scholar 

  11. Xu, B. et al. Advances of stem cell-laden hydrogels with biomimetic microenvironment for osteochondral repair. Front. Bioeng. Biotechnol. 8, 247 (2020).

    Google Scholar 

  12. Zhang, Z. et al. Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by Cofilin phosphorylation. Nat. Commun. 13, 6854 (2022).

    Google Scholar 

  13. Ke, W. et al. N-cadherin mimetic hydrogel enhances MSC chondrogenesis through cell metabolism. Acta Biomater. 150, 83–95 (2022).

    Google Scholar 

  14. Radice, G. L. N-cadherin-mediated adhesion and signaling from development to disease: lessons from mice. Prog Mol. Biol. Transl Sci. 116, 263–289 (2013).

    Google Scholar 

  15. Arai, F., Hosokawa, K., Toyama, H., Matsumoto, Y. & Suda, T. Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche. Ann. N Y Acad. Sci. 1266, 72–77 (2012).

    Google Scholar 

  16. Mrozik, K. M., Blaschuk, O. W., Cheong, C. M., Zannettino, A. C. W. & Vandyke, K. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 18, 939 (2018).

    Google Scholar 

  17. Qazi, T. H., Mooney, D. J., Duda, G. N. & Geissler, S. Niche-mimicking interactions in peptide-functionalized 3D hydrogels amplify mesenchymal stromal cell paracrine effects. Biomaterials 230, 119639 (2020).

    Google Scholar 

  18. Huang, M. S. et al. Viscoelastic N-cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices. Nat. Commun. 16, 5213 (2025).

    Google Scholar 

  19. Kapałczyńska, M. et al. 2D and 3D cell cultures – a comparison of different types of cancer cell cultures. Arch. Med. Sci. 14, 910–919 (2018).

    Google Scholar 

  20. Carter, K. et al. Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo. Acta Biomater. 99, 247–257 (2019).

    Google Scholar 

  21. Pan, Y. et al. Alternating 2D and 3D culture reduces cell size and extends the lifespan of placenta-derived MSCs. bioRxiv (2024).

  22. Dazzi, F., Lopes, L. & Weng, L. Mesenchymal stromal cells: A key player in ‘innate tolerance’? Immunology 137, 206 (2012).

    Google Scholar 

  23. Skibber, M. A., Noack, F. R. & Leach, J. K. Enhancing mesenchymal stromal cell potency: inflammatory licensing via mechanotransduction. Front. Immunol. 13, 874698 (2022).

    Google Scholar 

  24. Miceli, V. Use of priming strategies to advance the clinical application of mesenchymal stromal/stem cell-based therapy. World J. Stem Cells. 16, 7–20 (2024).

    Google Scholar 

  25. Thai, V. L., Mierswa, S., Griffin, K. H., Boerckel, J. D. & Leach, J. K. Mechanoregulation of MSC spheroid Immunomodulation. APL Bioeng. 8 (1), 016116 (2024).

    Google Scholar 

  26. Oas, R. G., Daugherty, R. L. & Gottardi, C. J. P120-catenin and β-catenin differentially regulate Cadherin adhesive function. Mol. Biol. Cell. 24, 704–714 (2013).

    Google Scholar 

  27. Jin, X., Lin, T., Wang, Y., Li, X. & Yang, Y. Functions of p120-catenin in physiology and diseases. Front. Mol. Biosci. 11, 1486576 (2024).

    Google Scholar 

  28. Nelson, W. J. & Nusse, R. Convergence of Wnt, β-Catenin, and Cadherin pathways. Science 303, 1483–1487 (2004).

    Google Scholar 

  29. Bienz, M. β-catenin: A Pivot between cell adhesion and Wnt signalling. Curr. Biol. 15, R44–R46 (2005).

    Google Scholar 

  30. Kourtidis, A., Ngok, S. P. & Anastasiadis, P. Z. p120 catenin: an essential regulator of Cadherin stability, adhesion-induced signaling, and cancer progression. Prog Mol. Biol. Transl Sci. 116, 409–432 (2013).

    Google Scholar 

  31. Murphy, M. B., Moncivais, K. & Caplan, A. I. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp. Mol. Med. 45, e54 (2013).

    Google Scholar 

  32. Chapman, H. A. Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration. Curr. Opin. Cell. Biol. 9, 714–724 (1997).

    Google Scholar 

  33. Ferrara, N., Gerber, H. P. & LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 9, 669–676 (2003).

    Google Scholar 

  34. Page-McCaw, A., Ewald, A. J. & Werb, Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell. Biol. 8, 221–233 (2007).

    Google Scholar 

  35. Duval, K. et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology 32, 266–277 (2017).

    Google Scholar 

  36. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Google Scholar 

  37. Ladoux, B. & Mège, R. M. Mechanobiology of collective cell behaviours. Nat. Rev. Mol. Cell. Biol. 18, 743–757 (2017).

    Google Scholar 

  38. Bauer, M. S. et al. Structural and mechanistic insights into mechanoactivation of focal adhesion kinase. Proc. Natl. Acad. Sci. U. S. A. 116, 6766–6774 (2019).

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