title: Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering.
abstract: Recently, it has been shown that tethered anti-BMP2 monoclonal antibodies (mAbs) can trap BMP ligands and thus provide BMP inductive signals for osteo-differentiation of progenitor cells. The objectives of this study were to: (1) develop a co-delivery system based on murine anti-BMP2 mAb-loaded alginate microspheres encapsulating human bone marrow mesenchymal stem cells (hBMMSCs); and (2) investigate osteogenic differentiation of encapsulated stem cells in alginate microspheres in vitro and in vivo. Alginate microspheres of 1 ± 0.1 mm diameter were fabricated with 2 × 10(6) hBMMSCs per mL of alginate. Critical-size calvarial defects (5 mm diameter) were created in immune-compromised mice and alginate microspheres preloaded with anti-BMP mAb encapsulating hBMMSCs were transplanted into defect sites. Alginate microspheres pre-loaded with isotype-matched non-specific antibody were used as the negative control. After 8 weeks, micro CT and histologic analyses were used to analyze bone formation. In vitro analysis demonstrated that anti-BMP2 mAbs tethered BMP2 ligands that can activate the BMP receptors on hBMMSCs. The co-delivery system described herein, significantly enhanced hBMMSC-mediated osteogenesis, as confirmed by the presence of BMP signal pathway-activated osteoblast determinants Runx2 and ALP. Our results highlight the importance of engineering the microenvironment for stem cells, and particularly the value of presenting inductive signals for osteo-differentiation of hBMMSCs by tethering BMP ligands using mAbs. This strategy of engineering the microenvironment with captured BMP signals is a promising modality for repair and regeneration of craniofacial, axial and appendicular bone defects.
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moshaverinia
authors.forename: Sahar
authors.initials: S
authors.lastname: Ansari
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.forename: Xingtian
authors.initials: X
authors.lastname: Xu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akiyama
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000328:Adult; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D055396:Bone Morphogenetic Protein 2 / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008863:Microspheres; D023822:Tissue Engineering / Q000379:methods*; D055815:Young Adult
chemical_list: D000464:Alginates; D000911:Antibodies, Monoclonal; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020723:Glucuronic Acid