title: Effect of Nano-HA/Collagen Composite Hydrogels on Osteogenic Behavior of Mesenchymal Stromal Cells.
abstract: This study aimed to comparatively evaluate the in vitro effect of nanosized hydroxyapatite and collagen (nHA/COL) based composite hydrogels (with different ratios of nHA and COL) on the behavior of human mesenchymal stromal cells (MSCs), isolated from either adipose tissue (AT-MSCs) or bone marrow (BM-MSCs). We hypothesized that (i) nHA/COL composite hydrogels would promote the osteogenic differentiation of MSCs in an nHA concentration dependent manner, and that (ii) AT-MSCs would show higher osteogenic potential compared to BM-MSCs, due to their earlier observed higher proliferation and osteogenic differentiation potential in 2D in vitro cultures [1]. The obtained results indicated that AT-MSCs show indeed high proliferation, differentiation and mineralization capacities in nHA/COL constructs compared to BM-MSCs, but this effect was irrespective of nHA concentration. Based on the results of alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein level, the osteogenic differentiation of BM-MSCs started in the beginning of the culture period and for AT-MSCs at the end of the culture period. At a molecular level, both cell types showed high expression of osteogenic markers (bone morphogenic protein 2 [BMP2], runt-related transcription factor 2 [RUNX2], OCN or COL1) in both an nHA concentration and time dependent manner. In conclusion, AT-MSCs demonstrated higher osteogenic potential in nHA/COL based 3D micro-environments compared to BM-MSCs, in which proliferation and osteogenic differentiation were highly promoted in a time dependent manner, irrespective of nHA amount in the constructs. The fact that AT-MSCs showed high proliferation and mineralization potential is appealing for their application in future pre-clinical research as an alternative cell source for BM-MSCs.
authors.affiliation: Department of Biomaterials, Radboudumc, Ph van Leijdenlaan 25, 6525 ex, Nijmegen, The Netherlands.
authors.forename: Astghik
authors.initials: A
authors.lastname: Hayrapetyan
authors.affiliation: Department of Biomaterials, Radboudumc, Ph van Leijdenlaan 25, 6525 ex, Nijmegen, The Netherlands.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bongio
authors.affiliation: Department of Biomaterials, Radboudumc, Ph van Leijdenlaan 25, 6525 ex, Nijmegen, The Netherlands.
authors.forename: Sander C G
authors.initials: SC
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Biomaterials, Radboudumc, Ph van Leijdenlaan 25, 6525 ex, Nijmegen, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: Department of Biomaterials, Radboudumc, Ph van Leijdenlaan 25, 6525 ex, Nijmegen, The Netherlands. jeroen.vandenbeucken@radboudumc.nl.
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D017886:Durapatite / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D020100:Hydrogels; D015675:Osteocalcin; D003094:Collagen; D017886:Durapatite; D000469:Alkaline Phosphatase
keywords: AT-MSCs; BM-MSCs; Calcium phosphate; Composite hydrogels; Osteogenic differentiation