Regulation of epithelial-mesenchymal cell-cell partners by complexes of paracrine signals and sulfated oligosaccharides

Zhang, Wencheng, Wauthier, Eliane, Xu, Yongmei, Su, Guowei, Caterson, Bruce ORCID: https://orcid.org/0000-0001-6016-0661, Overi, Diletta, Carpino, Guido, Gaudio, Eugenio, Liu, Jian and Reid, Lola M. 2027. Regulation of epithelial-mesenchymal cell-cell partners by complexes of paracrine signals and sulfated oligosaccharides. Biomaterials 336 , 124461. 10.1016/j.biomaterials.2026.124461

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Abstract

Complexes of paracrine signals and synthesized, sulfated oligosaccharides regulate expansion and/or differentiation of human epithelial-mesenchymal cell-cell partners with lineage-stage-specific distinctions exemplified in mature hepatocytes versus organoids of stem cells. Of a bank of 53 synthesized heparan sulfate-(HS)-oligosaccharides, 28 formed triggering complexes with selected paracrine signals. Of these, the 12-mer oligosaccharides proved representative for the biological effects of a specific chain chemistry. Optimized conditions for responses to complexes are: The complexes offer nuanced regulatory controls of growth and differentiation of organs and tissues. Representative triggering complexes [HS-oligosaccharide + paracrine signal] include ones regulating: Self-renewal: fibroblast growth factor-2 (FGF2) bound to an HS-oligosaccharide containing [NS2S] or WNT3A bound to [NS2S6S3S] Hypertrophy: vascular epithelial growth factor-A (VEGF-A) bound to an HS-oligosaccharide; containing [NS2S6S3S or NS2S6S]. Expansion in parallel with differentiation: various complexes with a paracrine signal and an oligosaccharide containing [NS2S3S6S]; representative paracrine signals include FGF2, hepatocyte growth factor (HGF), and others. Newly prepared, synthesized chondroitin sulfate-(CS)-oligosaccharides also form triggering complexes with biological responses requiring similar conditions as those for HS-oligosaccharides. Ongoing research efforts are surveying the specific biological responses to particular complexes of CS-oligosaccharides and paracrine signals.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Additional Information:	Corrigendum available 26/08/2026: https://doi.org/10.1016/j.biomaterials.2026.124556
Publisher:	Elsevier
ISSN:	0142-9612
Date of Acceptance:	13 July 2026
Last Modified:	01 Sep 2026 09:34
URI:	https://orca.cardiff.ac.uk/id/eprint/188514

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