title: BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects.
abstract: Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs.
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: He
authors.forename: Rosemary
authors.initials: R
authors.lastname: Dziak
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.forename: Keya
authors.initials: K
authors.lastname: Mao
authors.forename: Robert
authors.initials: R
authors.lastname: Genco
authors.forename: Mark
authors.initials: M
authors.lastname: Swihart
authors.forename: Debanjan
authors.initials: D
authors.lastname: Sarkar
authors.forename: Chunyi
authors.initials: C
authors.lastname: Li
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Stelios
authors.initials: S
authors.lastname: Andreadis
authors.forename: Shuying
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology*; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology; D051381:Rats; D012886:Skull / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D055396:Bone Morphogenetic Protein 2
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