Evaluation of Direct <i>In Vivo</i> Gene Transfer in an Equine Metacarpal <scp>IV</scp> Ostectomy Model Using an Adenoviral Vector Encoding the Bone Morphogenetic Protein‐2 and Protein‐7 Gene

Southwood, Louise L.; Kawcak, Christopher E.; Hidaka, Chisa; McIlwraith, C. Wayne; Werpy, Natasha M.; MacLeay, Jennifer M.; Frisbie, David D.

doi:10.1111/j.1532-950x.2011.00947.x

Cited by 12 publications

(40 citation statements)

References 52 publications

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“…(2) Ex vivo expedited techniques harvest and transduce using a single “same‐day” technique, providing fewer cells, and in cases where bone marrow aspirate concentrate (BMAC) are used, a very small population of BMDMSCs . (3) In vivo suspension techniques transfer a virus capable of transducing the native cell population, either directly, percutaneously at the completion of surgery, or within 2 weeks of surgery completion, and (4) Lyophilization of viral vectors to allografts allows selective transduction of cells that infiltrate the fracture callus, improving the biomechanical properties of allografts and their potential to undergo remodeling …”

Section: Discussionmentioning

confidence: 99%

“…17,18 (2) Ex vivo expedited techniques harvest and transduce using a single "same-day" technique, 19 providing fewer cells, and in cases where bone marrow aspirate concentrate (BMAC) are used, a very small population of BMDMSCs. 20 (3) In vivo suspension techniques transfer a virus capable of transducing the native cell population, either directly, 21 percutaneously at the completion of surgery, or within 2 weeks of surgery completion, 22,23 and (4) Lyophilization of viral vectors to allografts allows selective transduction of cells that infiltrate the fracture callus, improving the bio-mechanical properties of allografts and their potential to undergo remodeling. 8 All concerns considered, important clinical needs of equine clinical fracture cases are (1) that horses, in most cases, are operated on within 24 h of presentation; (2) horses would benefit from earlier biomechanical stability of the fracture environment aimed to decrease secondary complications, 24 and (3) a biologic, gene therapeutic approach may provide strong osteoinductive and osteogenic elements to equine fracture repair.…”

Section: Discussionmentioning

confidence: 99%

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Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

Ball

Phillips

McIlwraith

et al. 2019

Journal Orthopaedic Research

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Optimizing the environment of complex bone healing and improving treatment of catastrophic bone fractures and segmental bone defects remains an unmet clinical need both human and equine veterinary medical orthopaedics. The objective of this study was to determine whether scAAV‐equine‐BMP‐2 transduced cells would induce osteogenesis in equine bone marrow derived mesenchymal stem cells (BMDMSCs) in vitro, and if these cells could be cryopreserved in an effort to osteogenically prime them as an “off‐the‐shelf” gene therapeutic approach for fracture repair. Our study found that transgene expression is altered by cell expansion, as would be expected by a transduction resulting in episomal transgene expression, and that osteoinductive levels could still be achieved 5 days after recovery, and protein expression would continue up to 14 days after transduction. This is the first evidence that cryopreservation of genetically modified BMDMSCs would not alter the osteoinductive potential or clinical use of allogeneic donor cells in cases of equine fracture repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1310–1317, 2019.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

Ball

Phillips

McIlwraith

et al. 2019

Journal Orthopaedic Research

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“…However, the injection of AdBMP2 and Ad-BMP7 in the site of an osteotomy in 450 kg equines to induce osteogenesis after a 16-week evaluation did not show differences between the control and the transduced groups [38]. …”

Section: Discussionmentioning

confidence: 99%

Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis 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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“…69 Nevertheless, success was reported in some, but not all, studies of adenoviral delivery of BMP-2 or BMP-6 to horses. 70,71 …”

Section: Gene Therapy Progressmentioning

confidence: 99%

Gene therapy approaches to regenerating the musculoskeletal system

2015

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Injuries to the musculoskeletal system are common, debilitating and expensive. In many cases, healing is imperfect, which leads to chronic impairment. Gene transfer might improve repair and regeneration at sites of injury by enabling the local, sustained and potentially regulated expression of therapeutic gene products; such products include morphogens, growth factors and anti-inflammatory proteins. Proteins produced endogenously as a result of gene transfer are nascent molecules that have undergone post-translational modification. In addition, gene transfer offers particular advantages for the delivery of products with an intracellular site of action, such as transcription factors and noncoding RNAs, and proteins that need to be inserted into a cell compartment, such as a membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or ex vivo protocols using progenitor or differentiated cells. The first gene transfer clinical trials for osteoarthritis and cartilage repair have already been completed. Various bone-healing protocols are at an advanced stage of development, including studies with large animals, and human trials are envisaged. Other applications in the repair and regeneration of skeletal muscle, intervertebral disc, meniscus, ligament and tendon are in preclinical development. In addition to scientific, medical and safety considerations, clinical translation is constrained by social, financial and logistical issues.

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Evaluation of Direct In Vivo Gene Transfer in an Equine Metacarpal IV Ostectomy Model Using an Adenoviral Vector Encoding the Bone Morphogenetic Protein‐2 and Protein‐7 Gene

Abstract: Ad-hBMP-2/-7 did not improve bone healing in horses at 16 weeks.

Cited by 12 publications

References 52 publications

Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

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

Gene therapy approaches to regenerating the musculoskeletal system

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