The Effects of Lentiviral Gene Therapy With Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats

Miyazaki, Masashi; Sugiyama, Osamu; Tow, Benjamin; Zou, Jun; Morishita, Yuichiro; Wei, Feng; Napoli, Antonia Passarelli di; Sintuu, Chananit; Lieberman, Jay R.; Wang, Jeffrey C.

doi:10.1097/bsd.0b013e31814cf51d

Cited by 42 publications

(30 citation statements)

References 33 publications

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“…Lentiviruses are also able to transduce a wide variety of cells, including non-dividing cells, and can integrate into the genome to provide sustained gene expression. With respect to bone growth, Miyazaki et al (2008) showed that BMP-2-producing rat bone marrow cells created through lentiviral gene transfer induced sufficient spinal fusion in rats. Zhang et al (2002) reported that lentiviral vectors were able to transduce human bone marrow-derived stromal cells through many cell divisions and during differentiation into adipocytes.…”

Section: Discussionmentioning

confidence: 99%

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

Fu¹,

Diao²,

Shao³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Osteoporosis poses a major public health threat in aging societies. Adipose-derived stem cells (ADSCs) are multipotent adult stem cells that have the ability to yield mesenchymal stem cells, and have the potential to undergo osteogenesis and bone regeneration. Bone morphogenetic proteins (BMPs) have been demonstrated to upregulate bone gene expression after mechanical injury and to improve bone injury repair. This study aimed to produce BMP-2 expression in ADSCs by using lentiviral vectors. Subcutaneous adipose tissue from 4-week-old male Sprague-Dawley rats was used. Oil red O staining was used to detect adipocyte formation from ADSCs. Induction of ADSC osteogenesis was confirmed with Alizarin red S staining. The recombinant lenti-hBMP-2/ BMP-2 promotes chondrogenesis of rat adipose neo was constructed to infect ADSCs, BMP-2 expression was measured by immunoblotting analysis, and cellular alkaline phosphatase levels were examined. We found that >70% of ADSC cells could be induced to differentiate into osteocytes or adipocytes. Under osteogenic induction, ADSCs showed increased intracellular calcium deposition, the formation of calcium tubercles, and the disappearance of cellular structures in calcium tubercles. After infection of ADSCs by lenti-hBMP-2/neo, BMP-2 was expressed after doxycycline induction. We, thus, conclude that ADSCs maintain vigorous growth ex vivo and possess stem celllike properties. When infected with lenti-hBMP-2/neo, ADSCs can be induced to promote BMP-2 expression.

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Section: Discussionmentioning

confidence: 99%

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

Fu¹,

Diao²,

Shao³

et al. 2014

Genet. Mol. Res.

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“…Due to the short half-life and heterotopic ossification seen with locally administered BMP, studies have examined the use of gene therapy to increase BMP production at the site of bone defects and spinal fusions [15,[35][36][37]. In a goat model for ON, Tang and colleagues were able to show the formation of lamellar bone using a β-tricalcium phosphate (β-TCP) scaffold loaded with BMP-2 gene-modified MSCs [22].…”

Section: Animal Studies Investigating Bone Morphogenetic Proteins Formentioning

confidence: 99%

“…Bone regeneration is modulated by various cellular mediators including bone morphogenetic proteins (BMP), angiogenic growth factors, interleukins, and cytokines, all of which have been used to treat bone defects [13][14][15][16]. It is thought that through use of these agents alone or in combination with an operative procedure, healing of ON lesions can be enhanced (see Tables 1 and 2).…”

Section: Adjuvant Growth Factorsmentioning

confidence: 99%

Osteonecrosis of the femoral head: treatment with ancillary growth factors

Houdek

Wyles

Sierra

2015

Curr Rev Musculoskelet Med

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Osteonecrosis (ON) of the femoral head, also known as avascular necrosis (AVN) of the femoral head, is a progressive disease that predominantly affects younger patients. During early stage of ON, decompression of the femoral head has been commonly used to improve pain. The decompression has been augmented with nonvascularized or vascularized bone grafts, mesenchymal stems cells, and growth factors. The use of adjuvant growth factors to supplement the core decompression has mainly been limited to animal models in an attempt to regenerate the necrotic lesion of ON. Factors utilized include bone morphogenetic proteins, vascular endothelial growth factors, hepatocyte growth factors, fibroblast growth factors, granulocyte colonystimulating factors, and stem cells factors. In animal models, the use of these factors has been shown to increase bone formation and angiogenesis. Although promising, the use of these growth factors and cell-based therapies clinically remains limited.

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“…Various improvements have been implemented to ensure such safety [82,97,114], and gene therapy has been validated as a safe technique in preclinical animal experiments [13,30,43,64,70,99,101]. However, long-term results have not yet been elucidated, and further studies are required before these vectors can be used in clinical practice.…”

Section: Gene Therapymentioning

confidence: 99%

“…Host immunity destroys the transduced cells and reduces the effect of transgene expression. Recently, in order to compensate the disadvantage of adenoviral vectors, various viral vectors such as adeno-associated viral vector and lentiviral vector, have been tested [26,64,83].…”

Section: Gene Therapymentioning

confidence: 99%

An update on bone substitutes for spinal fusion

et al. 2009

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With the current advances in spinal surgery, an understanding of the precise biological mechanism of each bone substitute is necessary for inducing successful spinal fusion. In this review, the categories of bone substitutes include allografts, ceramics, demineralized bone matrix, osteoinductive factors, autogenous platelet concentrate, mesenchymal stem cells, and gene therapy. Further, clinical studies have been evaluated by their levels of evidence in order to elucidate the precise effect of the bone substitute employed and to establish clinical guidance. This article will review both clinical studies based on evidence and basic research in current advances in order to avoid as far as possible any chances of failure in the future and to understand cellular biology in novel technologies.

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The Effects of Lentiviral Gene Therapy With Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats

Abstract: The present study demonstrated that BMP-2-producing RBMCs, created through lentiviral gene transfer, induced sufficient spinal fusion. The use of lentiviral vectors that contain the cDNA for BMP-2 will be a novel and promising approach for a spinal fusion strategy.

Cited by 42 publications

References 33 publications

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

Osteonecrosis of the femoral head: treatment with ancillary growth factors

An update on bone substitutes for spinal fusion

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