Structural Bone Allograft Combined with Genetically Engineered Mesenchymal Stem Cells As a Novel Platform for Bone Tissue Engineering

Xie, Chao; Reynolds, David G.; Awad, Hani A.; Rubery, Paul T.; Pelled, Gadi; Gazit, Dan; Guldberg, Robert E.; Schwarz, Edward M.; O’Keefe, Regis J.

doi:10.1089/ten.2007.13.ft-312

Cited by 14 publications

(18 citation statements)

References 34 publications

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“…Recently, advances in gene delivery techniques have made possible the use of BMPs in combination with osteogenic cells to treat bone allografts with encouraging results in allograft healing and integration. 5,34,48,49 A combination of these therapies is a promising strategy that improves the osteogenic and osteoinductive potential of structural bone allografts.…”

Section: Discussionmentioning

confidence: 99%

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Cornejo

Sahar

Stephenson

et al. 2012

Tissue Engineering Part A

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The use of processed bone allograft to repair large osseous defects of the skull has been limited, given that it lacks the osteogenic cellularity and intrinsic vascular supply which are essential elements for successful graft healing and, at the same time, the areas to be targeted through tissue-engineering applications. In this study, we investigated the effect of predifferentiated rat adipose tissue-derived osteoblastic cells (OBs) and endothelial cells (ECs) on calvarial bone allograft healing and vascularization using an orthotopic critical-sized calvarial defect model. For this purpose, thirty-seven 8 mm critical calvarial defects in Lewis rats were treated with bone allografts seeded with no cells, undifferentiated adipose tissue-derived stem cells (ASC), OBs, ECs, and OBs and ECs simultaneously. After 8 weeks, the bone volume and mineral density were calculated using microcomputed tomography and the microvessel formation using immunohistochemical staining and imaging software. The amount of bone within the 8 mm defect was significantly higher for the allografts treated with ECs compared with the allografts treated with OBs (p=0.05) and simultaneously with the two cell lineages (p=0.02). There were no significant differences in bone formation between the latter two groups and the control groups (allografts treated with no cells and undifferentiated ASC). There were no significant differences in bone mineral density among the groups. The amount of microvessels was significantly higher in the group treated with ECs relative to all groups (p=< 0.05). Our results show that the implantation of ASC-derived ECs improves the vascularization of calvarial bone allografts at 8 weeks after treatment. This cell-based vascularization strategy can be used to improve the paucity of perfusion in allogenic bone implants. However, in this study, the treatment of allografts with OBs alone or in combination with ECs did not support bone formation or vascularization.

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Section: Discussionmentioning

confidence: 99%

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Cornejo

Sahar

Stephenson

et al. 2012

Tissue Engineering Part A

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“…Indeed, it has also been documented that by seeding BMP2 modified cells directly onto an allograft, cartilaginous tissue and a new cortical shell were formed resulting in bridging of a segmental defect. However, this did not completely mimic an autograft as slower resorption of the graft was observed [103]. More recently it has been reported that BM-MSC cell sheets can act as an engineered periosteum and promote bone callus formation during allograft healing [104], while PDC cell sheets may have applications in tendon-bone healing [105].…”

Section: Tissue Engineering Strategies Mimicking the Periosteum In Itmentioning

confidence: 99%

Uncovering the periosteum for skeletal regeneration: The stem cell that lies beneath

Roberts

Gastel

Carmeliet

et al. 2015

Bone

209

186

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The cartilage- and bone-forming properties of the periosteum have long since been recognized. As one of the major sources of skeletal progenitor cells, the periosteum plays a crucial role not only in bone development and growth, but also during bone fracture healing. Aided by the continuous expansion of tools and techniques, we are now starting to acquire more insight into the specific role and regulation of periosteal cells. From a therapeutic point of view, the periosteum has attracted much attention as a cell source for bone tissue engineering purposes. This interest derives not only from the physiological role of the periosteum during bone repair, but is also supported by the unique properties and marked bone-forming potential of expanded periosteum-derived cells. We provide an overview of the current knowledge of periosteal cell biology, focusing on the cellular composition and molecular regulation of this remarkable tissue, as well as the application of periosteum-derived cells in regenerative medicine approaches. This article is part of a Special Issue entitled "Stem Cells and Bone".

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“…For these studies we chose to use the C3H10T1/2 cell line, since it is representative of the mesenchymal progenitor cell targets of the gene therapy and has been demonstrated to mediate efficient bone formation in vivo when transfected with osteogenic genes [22,23]. (Fig.…”

Section: Effects Of Surface Demineralization On Raav-luc Transductionmentioning

confidence: 99%

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings

et al. 2008

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Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; p<0.001) increase in percent surface area coating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

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Structural Bone Allograft Combined with Genetically Engineered Mesenchymal Stem Cells As a Novel Platform for Bone Tissue Engineering

Cited by 14 publications

References 34 publications

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Uncovering the periosteum for skeletal regeneration: The stem cell that lies beneath

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings

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