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Sulfation of Glycosaminoglycan Hydrogels Instructs Cell Fate and Chondral versus Endochondral Lineage Decision of Skeletal Stem Cells In Vivo
Author(s) -
Chasan Safak,
Hesse Eliane,
Atallah Passant,
Gerstner Matthias,
Diederichs Solvig,
Schenker Astrid,
Grobe Kay,
Werner Carsten,
Richter Wiltrud
Publication year - 2022
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202109176
Subject(s) - microbiology and biotechnology , endochondral ossification , biology , wnt signaling pathway , cell fate determination , stem cell , mesenchymal stem cell , cellular differentiation , glycosaminoglycan , cartilage , signal transduction , anatomy , biochemistry , gene , transcription factor
Exit from multipotency and lineage commitment of mesenchymal stroma cells (MSC) depends on microenvironmental cues from the stem‐cell niche but steering cell fate into the desired lineage in vivo remains a challenge. Increasing evidence suggests that glycosaminoglycans (GAGs) can be used to activate or sequester growth factors with the specific action depending on sulfation levels. It is postulated that differentially sulfated biomaterials can aid developmental lineage instruction of MSC to guide tissue morphogenesis in vivo. By application of a new injectable TGFβ‐loaded heparin‐PEG‐hydrogel the authors here gain the ability to control skeletal stem‐cell fate in vivo down the chondral versus the endochondral pathway depending on the sulfation status. High sulfation allows for long‐term TGFβ‐retention and silencing of Hedgehog‐, BMP‐, and WNT‐pathways installing prochondrogenic and antihypertrophic cues which permitted in vivo growth of permanent, collagen‐type‐II‐rich neocartilage with long‐term resistance to calcification and bone formation. Selective 6‐ O / N ‐desulfation of heparin supports Hedgehog/BMP/WNT‐signaling switching lineage commitment into endochondral differentiation with strong hypertrophic/osteogenic marker expression and tissue calcification. This work identifies GAG sulfation as a crucial niche instruction signal to determine the chondral stem‐cell fate via silencing of prohypertrophic pathways, providing the first proof‐of‐principle on how GAG modification‐patterns can determine cell lineage‐choice during tissue morphogenesis in vivo.