title: Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue-Like Environments in PEG Hydrogels.
abstract: In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)-based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP-2, the treatment with FGF-2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM-MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow-like 3D tissue constructs.
authors.affiliation: Department of Obstetrics, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blache
authors.affiliation: Department of Obstetrics, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Metzger
authors.affiliation: Department of Obstetrics, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: Queralt
authors.initials: Q
authors.lastname: Vallmajo-Martin
authors.affiliation: Department of Biomedicine and Department of Surgery, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012, Bern, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
authors.affiliation: Department of Obstetrics, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Ehrbar
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D002470:Cell Survival; D018920:Coculture Techniques; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D011092:Polyethylene Glycols / Q000737:chemistry*; D023822:Tissue Engineering
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols
keywords: 3D tissue model; mesenchymal stem cells; microvascularization; osteogenesis; synthetic hydrogel