title: Mesenchymal Stem Cells Within Gelatin/CaSO4 Scaffolds Treated Ex Vivo with Low Doses of BMP-2 and Wnt3a Increase Bone Regeneration.
abstract: The delivery of osteogenic factors is a proven therapeutic strategy to promote bone regeneration. Bone morphogenetic proteins (BMPs) constitute a family of cytokines with well-known osteogenic and bone regenerative abilities. However, clinical uses of BMPs require high doses that have been associated with complications such as osteolysis, ectopic bone formation, or hematoma formation. In the present work, we sought to improve bone tissue engineering through an approach that combines the use of bone marrow-derived mesenchymal stem cells (BMMSCs), composite scaffolds, and osteoinductive agents. We employed a composite gelatin/CaSO4 scaffold that allows for an early expansion of seeded BMMSCs, which is followed by an increased level of osteogenic differentiation after 10 days in culture. Furthermore, this scaffold enhanced bone formation by BMMSCs in a mouse model of critical-sized calvarial defect. More importantly, our results demonstrate that ex vivo pretreatment of BMMSCs with low amounts of BMP-2 (2 nM) and Wnt3a (50 ng/mL) for 24 h cooperatively increases the expression of osteogenic markers in vitro and bone regeneration in the critical-sized calvarial defect mouse model. These data provide a strong rationale for the development of an ex vivo cooperative use of BMP-2 and Wnt3a. Osteogenic factor cooperation might be applied to reduce the required amount of growth factors while obtaining higher therapeutic effects.
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Rubén
authors.initials: R
authors.lastname: Aquino-Martínez
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rodríguez-Carballo
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gámez
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Natalia
authors.initials: N
authors.lastname: Artigas
authors.affiliation: 2 Unitat d'Anatomia i Embriologia Humana, Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Patricia
authors.initials: P
authors.lastname: Carvalho-Lobato
authors.affiliation: 2 Unitat d'Anatomia i Embriologia Humana, Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manzanares-Céspedes
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rosa
authors.affiliation: 1 Departament de Ciències Fisiològiques II, Universitat de Barcelona , IDIBELL, L'Hospitalet de Llobregat, Spain .
authors.forename: Francesc
authors.initials: F
authors.lastname: Ventura
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002133:Calcium Sulfate / Q000494:pharmacology*; D005780:Gelatin / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D054457:Tissue Scaffolds; D060509:Wnt3A Protein / Q000494:pharmacology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D005780:Gelatin; D002133:Calcium Sulfate