Human Bone Morphogenetic Protein 2–Transduced Mesenchymal Stem Cells Improve Bone Regeneration in a Model of Mandible Distraction Surgery

Castro-Góvea, Yanko; Cervantes-Kardasch, Victor Hugo; Borrego‐Soto, Gissela; Martı́nez-Rodrı́guez, Herminia Guadalupe; Espinoza-Juarez, Marcela A.; Romero-Díaz, Viktor J; Marino-Martínez, Iván Alberto; Robles-Zamora, Alejandro; Álvarez-Lozano, Eduardo; Padilla‐Rivas, Gerardo R.; Ortı́z-López, Rocio; Lara‐Arias, Jorge; Vázquez-Juárez, José; Rojas-Martı́nez, Augusto

doi:10.1097/scs.0b013e318240fe9b

Cited by 46 publications

(53 citation statements)

References 15 publications

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“…Dong and colleagues reported that complete bone healing was achieved using MSCs transduced with a recombinant adenovirus AdCbfa1a at 12 weeks after a lesion to the right radius in the front leg in rabbits [39]. In the canine model where the implant with MSCs transduced with AdBMP2/AdBMP7 was previously tested, radiographic followup showed complete healing in the treated jaw at week 6 after distraction [23]. These data indicate a marked reduction in bone healing time when genetically modified MSCs are used.…”

Section: Discussionmentioning

confidence: 99%

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Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures inOvis aries

Hernandez-Hurtado

Borrego‐Soto

Marino-Martínez

et al. 2016

Stem Cells International

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Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

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Section: Discussionmentioning

confidence: 99%

“…The implant was constituted by bone marrow MSCs transduced with BMP2 and embedded in DBM [23]. For the present report, the challenge was to repair a major lesion in the tibia of a sheep model.…”

Section: Introductionmentioning

confidence: 99%

Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures inOvis aries

Hernandez-Hurtado

Borrego‐Soto

Marino-Martínez

et al. 2016

Stem Cells International

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“…This abnormality occurs in humans [2-8], dogs [9-40], cats [32,41-44], horses [45], cattle [46], goats [47], sheep [48] buffalo [49] and camels [50]. A review of canine cases is presented in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Multiple dermoid sinuses of type Vb and IIIb on the head of a Saint Bernard dog

et al. 2013

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Dermoid sinus, a congenital malformation of neural tube development, has been reported in humans and several animal species including dogs. It is typically found in the dorsal midline and commonly occurs in the Rhodesian Ridgeback breed. A case of multiple dermoid sinuses in the fronto-occipital region is described. An 11-month-old, intact female Saint Bernard dog was presented with a 2 day history of discharge from a large irregular subcutaneous mass in the fronto-occipital region. The dog was otherwise healthy. The dog had two circular skin lesions (approximately 4 × 4 and 4 × 2 cm diameter) surrounded by multiple irregular elevated masses. The masses had multiple small openings on the skin surface with tufts of hair protruding from the apertures. The masses were surgically removed, and the diagnosis of multiple dermoid sinuses was confirmed by histological examination. Histopathological examination showed multiple, variably sized, spherical to tubular cysts expanding the dermis and subcutis. Cysts were filled with hair shafts and lamellar keratin and were lined by a stratified squamous epithelium. Sebaceous and apocrine gland adnexal structures were also observed. To the best of our knowledge, this is the first reported case of multiple dermoid sinuses of two different types in the head of a Saint Bernard dog.

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“…Bone morphogenetic protein 2 (BMP-2) plays an important role in regulating osteoblast differentiation and subsequent bone formation (21-23). However, TNF-α can restrain BMP-2 signaling in osteoblastic differentiation (24-26).…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro

Guo

Sun

et al. 2013

Braz J Med Biol Res

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Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.

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Human Bone Morphogenetic Protein 2–Transduced Mesenchymal Stem Cells Improve Bone Regeneration in a Model of Mandible Distraction Surgery

Abstract: We demonstrated acceleration of osteogenesis in a dog model for bone distraction by using an implant of BMP-2 modified MSCs. These results are helpful for future clinical trials of mandible bone distraction.

Cited by 46 publications

References 15 publications

Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures inOvis aries

Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures inOvis aries

Multiple dermoid sinuses of type Vb and IIIb on the head of a Saint Bernard dog

Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro

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