BMPs and Gene Therapy for Spinal Fusion

Sandhu, Harvinder S.; Boden, Scott D.; An, Howard; Kang, James D.; Weinstein, James Neil

doi:10.1097/01.brs.0000076903.10966.86

Cited by 11 publications

(5 citation statements)

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“…Recombinant BMPs have been shown to reliably induce bone formation in numerous animal models 8. In fact, recombinant human BMP2 and BMP7 are currently approved for clinical use in select spine procedures 9–11. In addition, other BMPs are being evaluated in human clinical trials 11, 12.…”

Section: Introductionmentioning

confidence: 99%

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Ex Vivo Transfer of the Hoxc-8-interacting Domain of Smad1 by a Tropism-modified Adenoviral Vector Results in Efficient Bone Formation in a Rabbit Model of Spinal Fusion

Douglas

Rivera

Lyons³

et al. 2010

Journal of Spinal Disorders &Amp; Techniques

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Study Design-Ex vivo gene transfer for spinal fusion.Objective-This study aimed to evaluate ex vivo transfer of the nuclear-localized Hoxc-8interacting domain of Smad1 (termed Smad1C) to rabbit bone marrow stromal cells (BMSCs) by a tropism-modified human adenovirus serotype 5 (Ad5) vector as a novel therapeutic approach for spinal fusion.Summary of Background Data-Novel approaches are needed to improve the success of bone union after spinal fusion. One such approach is the ex vivo transfer of a gene encoding an osteoinductive factor to BMSCs which are subsequently reimplanted into the host. We have previously shown that heterologous expression of the Hoxc-interacting domain of Smad1 in the nuclei of osteoblast precursor cells is able to stimulate the expression of genes related to osteoblast differentiation and induce osteogenesis in vivo. Gene delivery vehicles based on human Ad5 are well-suited for gene transfer for spinal fusion because they can mediate high-level, short-term gene expression. However, Ad5-based vectors with native tropism poorly transduce BMSCs, necessitating the use of vectors with modified tropism to achieve efficient gene transfer.Methods-The gene encoding Smad1C was transferred to rabbit BMSCs by an Ad5 vector with native tropism or a vector retargeted to av integrins, which are abundantly expressed on rabbit BMSCs. Transduced BMSCs were maintained in osteoblastic differentiation medium for thirty days. Alkaline phosphatase activity was determined and cells stained for calcium deposition. As positive controls for osteogenesis, we employed Ad5 vectors expressing bone morphogenetic protein 2. As negative controls, BMSCs were mock-transduced or transduced with an Ad5 vector expressing β- In an immunocompetent rabbit model of spinal fusion, transduced BMSCs were coated onto absorbable gelatin sponge and implanted between decorticated transverse processes L6 and L7 of 8-week-old female New Zealand white rabbits. Animals were sacrificed 4 weeks post-implantation of the sponges, the fusion masses harvested and the area of new bone quantified using image analysis software. Results-The

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Section: Introductionmentioning

confidence: 99%

“…In fact, recombinant human BMP2 and BMP7 are currently approved for clinical use in select spine procedures 9–11. In addition, other BMPs are being evaluated in human clinical trials 11, 12. However, the use of recombinant osteoinductive proteins to augment bone formation suffers from a number of limitations.…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo Transfer of the Hoxc-8-interacting Domain of Smad1 by a Tropism-modified Adenoviral Vector Results in Efficient Bone Formation in a Rabbit Model of Spinal Fusion

Douglas

Rivera

Lyons³

et al. 2010

Journal of Spinal Disorders &Amp; Techniques

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“…18 The INFUSE Bone Graft (Medtronic Sofamor Danek, Minneapolis, MN) combines rhBMP-2 with an absorbable collagen sponge to induce osteogenesis. 19 The Food and Drug Administration has approved the use of a type-I collagen sponge enhanced with rhBMP-2 in combination with a tapered, threaded fusion cage (LT-CAGE; Medtronic Sofamor Danek) for the treatment of lumbar degenerative disc disease.…”

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confidence: 99%

Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion

Shields

Raque²,

Glassman³

et al. 2006

Spine

631

460

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A significant rate of complications resulted after the use of a high dose of INFUSE in anterior cervical fusions. We hypothesize that in the cervical area, the putative inflammatory effect that contributes to the effectiveness of INFUSE in inducing fusion may spread to adjacent critical structures and lead to increased postoperative morbidity. A thorough investigation is warranted to determine the optimal dose of rhBMP-2 that will promote cervical fusion and minimize complications.

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“…Пðè-мåíåíèå ãåííîé òåðàïèè ñ äëèòåëüíîé ïðîäóêöèåé фàêòîðîâ ðîñòà â êîíêðåòíîм мåñòå îòêðыâàåò ñëå-äóющèé шàã ê ñîâåðшåíñòâîâàíèю бèîòåхíîëîãèè ñïîíäèëîäåзà [31,38].…”

Section: практически все возможные хирургические методы лечения дегенunclassified

Gene therapy genetic aspects and possibilities for degenerative diseases of intervertebral disks treatment

Pedachenko¹,

Horbatyuk²

2008

Ukr Neurosurg J

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Â íàчàëå 90-х ãîäîâ ïðîшëîãî ñòîëåòèя èíòåíñèâíîå ðàзâèòèå мîëåêóëяðíîé бèîëîãèè è òêàíåâîé èíaeåíåðèè ïîзâîëèëî èзóчèòü âëèяíèå фàêòîðîâ ðîñòà íà êëåòêè мåaeïîзâîíêîâîãî äèñêà (МÄ). Â ïîñëåäíèå íåñêîëüêî ëåò ïîяâèëîñü бîëüшîå чèñëî эêñïåðèмåíòàëüíых èññëå-äîâàíèé, ïîñâящåííых èñïîëüзîâàíèю фàêòîðîâ ðîñòà, ñàмîñòîяòåëüíî èëè â ñîчåòàíèè ñ ãåííîé òåðàïèåé äëя бèîëîãèчåñêîé ðåãåíåðàöèè МÄ. Изóчåíèå âîзмîaeíîñòåé ãåííîé òåðàïèè ñòàíîâèòñя âñå бîëåå èíòåðåñíым è ïåðñïåêòèâíым, ïîñêîëüêó ïîòåíöèàëüíî ïîяâèëàñü âîз-мîaeíîñòü íå òîëüêî îñòàíîâèòü ïðîãðåññèðîâàíèå äåãåíåðàöèè МÄ, íî è ðåãåíåðèðîâàòü åãî. Пîêàзàíы îñíîâíыå ïðèíöèïы è ïðåäïîñыëêè ê èзóчåíèю äàííîãî мåòîäà, îïèñàíы îñíîâíыå эêñïåðèмåíòàëüíыå è êëèíèчåñêèå èññëåäîâàíèя, ïðîâåäåííыå ê íàñòîящåмó âðåмåíè. Пîзè-òèâíыå ðåзóëüòàòы ïðîâåäåííых èññëåäîâàíèé äàюò îñíîâàíèå ïðîãíîзèðîâàòü ïåðñïåêòèâы â хèðóðãèè äåãåíåðàòèâíî-äèñòðîфèчåñêèх зàбîëåâàíèé ïîзâîíîчíèêà ñ ïðèмåíåíèåм мèíè-èíâàзèâíых òåхíîëîãèé, чòî бóäåò ñïîñîбñòâîâàòü ïîâышåíèю åå эффåêòèâíîñòè.Кëючåâыå ñëîâà: дегенерация межпозвонкового диска, миниинвазивная хирургия, биотехнологии, факторы роста, генная терапия.

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BMPs and Gene Therapy for Spinal Fusion

Cited by 11 publications

References 0 publications

Ex Vivo Transfer of the Hoxc-8-interacting Domain of Smad1 by a Tropism-modified Adenoviral Vector Results in Efficient Bone Formation in a Rabbit Model of Spinal Fusion

Ex Vivo Transfer of the Hoxc-8-interacting Domain of Smad1 by a Tropism-modified Adenoviral Vector Results in Efficient Bone Formation in a Rabbit Model of Spinal Fusion

Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion

Gene therapy genetic aspects and possibilities for degenerative diseases of intervertebral disks treatment

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