Combining biomimetic collagen/hyaluronan hydrogels with discogenic growth factors promotes mesenchymal stroma cell differentiation into Nucleus Pulposus like cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biomaterials Science Année : 2023

Combining biomimetic collagen/hyaluronan hydrogels with discogenic growth factors promotes mesenchymal stroma cell differentiation into Nucleus Pulposus like cells

Prince David Okoro
  • Fonction : Auteur
  • PersonId : 1300240
Antoine Frayssinet
  • Fonction : Auteur
  • PersonId : 1300241
Stéphanie de Oliveira
  • Fonction : Auteur
  • PersonId : 1300242
Léa Rouquier
Esther Potier

Résumé

Based on stem cell injection into degenerated Nucleus Pulposus (NP), novel treatments for intervertebral disc (IVD) regeneration were disappointing because of cell leakage or inappropriate cell differentiation. In this study, we hypothesized that mesenchymal stroma cells encapsulated within injectable hydrogels possessing adequate physico-chemical properties would differentiate into NP like cells. Composite hydrogels consisting of type I collagen and tyramine-substituted hyaluronic acid (THA) were formed to mimic the NP physico-chemical properties. Human bone marrow derived mesenchymal stroma cells (BM-MSCs) were encapsulated within hydrogels and cultivated in proliferation medium (supplemented with 10% fetal bovine serum) or differentiation medium (supplemented with GDF5 and TGFβ1) over 28 days. Unlike pure collagen, collagen/THA composite hydrogels were stable over 28 days in culture. In proliferation medium, cell viability within pure collagen hydrogels was high whereas that in composite and pure THA hydrogels was lower due to the weaker cell adhesion. Nonetheless, BM-MSCs proliferated in all hydrogels. In composite hydrogels, cells exhibited a rounded morphology similar to NP cells. The differentiation medium did not impact hydrogel stability, cell morphology but negatively impact cell viability in pure collagen hydrogels. A high THA content within hydrogels promoted the gene expression of NP markers such as collagen II, aggrecan, SOX9 and Cytokeratin 18 at day 28. The differentiation medium potentialized this effect with an earlier and higher expression of these NP markers. Taken together, these results show that physico-chemical properties of collagen/THA composite hydrogels and GDF5/TGFβ1 act in synergy to promote the differentiation of BM-MSCs into NP like cells.
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Dates et versions

hal-04261067 , version 1 (26-10-2023)

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Prince David Okoro, Antoine Frayssinet, Stéphanie de Oliveira, Léa Rouquier, Gregor Milkosic, et al.. Combining biomimetic collagen/hyaluronan hydrogels with discogenic growth factors promotes mesenchymal stroma cell differentiation into Nucleus Pulposus like cells. Biomaterials Science, In press, Injectable Hydrogels, ⟨10.1039/D3BM01025B⟩. ⟨hal-04261067⟩
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