Co-Encapsulation of Anti-BMP2 Monoclonal Antibody and Mesenchymal Stem Cells in Alginate Microspheres for Bone Tissue Engineering

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Departmental Papers (Dental)
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Alginate hydrogel
Mesenchymal stem cell-mediated bone regeneration
Cells encapsulation
Anti-BMP2 monoclonal antibodies
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Moshaverinia, Alireza
Ansari, Sahar
Chen, Chider
Xu, Xingtian
Akiyama, Kentaro
Snead, Malcolm L.
Zadeh, Homayoun H.
Shi, Songtao

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 × 106 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 was used as the negative control. After 8 weeks, micro CT and histologic analysis 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.

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At the time of publication, author Chider Chen was affiliated with the University of Southern California. Currently, he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
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