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 invitro and invivo. Alginate microspheres of 1±0.1mm diameter were fabricated with 2×106 hBMMSCs per mL of alginate. Critical-size calvarial defects (5mm 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. Invitro 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.
| Original language | English |
|---|---|
| Pages (from-to) | 6572-6579 |
| Number of pages | 8 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - Sep 2013 |
| Externally published | Yes |
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Keywords
- Alginate hydrogel
- Anti-BMP2 monoclonal antibodies
- Cells encapsulation
- Mesenchymal stem cell-mediated bone regeneration
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering. / Moshaverinia, Alireza; Ansari, Sahar; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Snead, Malcolm L.; Zadeh, Homayoun H.; Shi, Songtao.
In: Biomaterials, Vol. 34, No. 28, 09.2013, p. 6572-6579.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering
AU - Moshaverinia, Alireza
AU - Ansari, Sahar
AU - Chen, Chider
AU - Xu, Xingtian
AU - Akiyama, Kentaro
AU - Snead, Malcolm L.
AU - Zadeh, Homayoun H.
AU - Shi, Songtao
PY - 2013/9
Y1 - 2013/9
N2 - 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 invitro and invivo. Alginate microspheres of 1±0.1mm diameter were fabricated with 2×106 hBMMSCs per mL of alginate. Critical-size calvarial defects (5mm 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. Invitro 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.
AB - 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 invitro and invivo. Alginate microspheres of 1±0.1mm diameter were fabricated with 2×106 hBMMSCs per mL of alginate. Critical-size calvarial defects (5mm 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. Invitro 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.
KW - Alginate hydrogel
KW - Anti-BMP2 monoclonal antibodies
KW - Cells encapsulation
KW - Mesenchymal stem cell-mediated bone regeneration
UR - http://www.scopus.com/inward/record.url?scp=84879464132&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879464132&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.05.048
DO - 10.1016/j.biomaterials.2013.05.048
M3 - Article
C2 - 23773817
AN - SCOPUS:84879464132
VL - 34
SP - 6572
EP - 6579
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 28
ER -