Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes

Park, J; Ries, Jutta; Gelse, Kolja; Kloss, Frank; Mark, Klaus von der; Wiltfang, Joerg; Neukam, Friedrich Wilhelm; Schneider, Holm

doi:10.1038/sj.gt.3301960

Cited by 211 publications

(167 citation statements)

References 39 publications

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“…BMP-2, approved by Food and Drug Administration (FDA) for clinical practice, is the most potent member in promoting bone and cartilage development and therefore wins a popular choice for MSCs-based BTE (Lieberman et al, 1998;Lieberman et al, 1999;Lou et al, 1999;Turgeman et al, 2001;Olmsted-Davis et al, 2002;Blum et al, 2003;Gugala et al, 2003;Park et al, 2003;Riew et al, 2003;Tsuda et al, 2003;Kumar et al, 2004;Hasharoni et al, 2005;Egermann et al, 2006;Feeley et al, 2006). The BMP-2-modified MSCs are proven to increase the alkaline phosphatase (ALP) activity, mineralization, and cell proliferation in vitro and induce ectopic bone formation, heal critical size bone defect, repair fracture, and trigger spinal fusion in vivo (Lou et al, 1999;Moutsatsos et al, 2001;Turgeman et al, 2001;Blum et al, 2003;Park et al, 2003;Riew et al, 2003;Tsuda et al, 2003;Hasharoni et al, 2005;Egermann et al, 2006;Feeley et al, 2006). BMP-7 plays a key role in osteoblast differentiation, and there is only one study in which MSCs are engineered with BMP-7.…”

Section: Applicable Genes For Mscs Modificationmentioning

confidence: 99%

“…Although there are remarkable improvements in its transfect efficiency in recent years, the nonviral vectors remain less efficient in delivery than viral vectors. Although BMP-7 and BMP-2 gene have been successfully engineered into MSCs via liposomes (Park et al, 2003;Hu et al, 2007), further optimization of liposome or other nonviral formulations is still needed.…”

Section: Selection Of Vectorsmentioning

confidence: 99%

“…Adenovirus vector is one of the most popular vectors for MSC gene therapy aimed at BTE Dumont et al, 2002;Olmsted-Davis et al, 2002;Blum et al, 2003;Dayoub et al, 2003;Gugala et al, 2003;Li et al, 2003;Park et al, 2003;Riew et al, 2003;Sugiyama et al, 2003;Tsuda et al, 2003;Yang et al, 2003;Kumar et al, 2004;Zheng et al, 2004;Zhao et al, 2005;Egermann et al, 2006;Feeley et al, 2006;Zachos et al, 2006). Adenovirus vector is characterized by efficient transduction of quiescent cells and a relatively high capacity for transgene insertion.…”

Section: Selection Of Vectorsmentioning

confidence: 99%

“…An optimal scaffold should provide genetically modified MSCs with the appropriate environment for attachment, proliferation, and differentiation, preventing them from migrating into other places of the body. The scaffold may be soluble for direct injection or solid for surgical implantation (Peng et al, 2001;Turgeman et al, 2001;Blum et al, 2003;Park et al, 2003;Rose et al, 2003;Tsuda et al, 2003;Feeley et al, 2006). Genetically engineered MSCs have the ability to induce bone regeneration not only through paracrine secretion of growth factors to adjacent cells but also by an autocrine effect on MSCs themselves to promote their osteogenic differentiation (Gazit et al, 1999).…”

Section: Cell-based Btementioning

confidence: 99%

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Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Hong

Chen²,

et al. 2010

The Anatomical Record

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Bone grafting is crucial in the surgical treatment of bone defects and nonunion fractures. Autogenous bone, allogenous bone, and biomaterial scaffold are three main sources of bone grafts. The biomaterial scaffold, both natural and synthetic, is widely accessible but weak in osteogenic potential. One approach to solve this problem is cell-based bone tissue engineering (BTE), established by growing living osteogenic cells on scaffold in vitro to build up its osteoinducitive capability. Mesenchymal stem cell (MSC) is suitable for use in cell-based BTE, but it remains a considerable challenge to induce MSCs to form solely bone and while preventing MSCs from differentiating into fats, muscles, and possibly neural elements in vivo. Recently, there is a drastic rise in use of genetically engineered MSCs, which can secrete growth factors or alter the transcription level, leading to osteoblast lineage commitment, bone formation, fracture repair, and spinal fusion. In this article, we reviewed the literatures regarding applications of genetically engineered MSCs in BTE. We addressed the currently applicable genes and candidate genes for MSCs modification, transduction efficiency and safety issues of the transfect vectors, and administration routes, and we briefly described in vivo tracking and potential clinical application of the genetically modified MSCs in BTE. Anat Rec, 293:531-537, 2010. V V C 2009 Wiley-Liss, Inc.

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Section: Applicable Genes For Mscs Modificationmentioning

confidence: 99%

Section: Selection Of Vectorsmentioning

confidence: 99%

Section: Selection Of Vectorsmentioning

confidence: 99%

Section: Cell-based Btementioning

confidence: 99%

See 2 more Smart Citations

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Hong

Chen²,

et al. 2010

The Anatomical Record

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“…Nonviral gene delivery systems seem to be offering the advantage of relative simplicity of preparation, avoidance of the size constraints of viral packaging, reduced toxicity and immunogenicity, and a generally advantageous safety profile. 13,[25][26][27][28][29][30] The main problem of nonviral gene approach, however, is the relatively low and transient expression of the transferred gene. On the other hand, conventional plasmid-based eukaryotic expression vectors do not replicate and therefore are not retained in the nucleus of the rapidly dividing cells, and as a consequence the plasmid DNA is rapidly diluted.…”

Section: Introductionmentioning

confidence: 99%

Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells

et al. 2008

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Synthetic oligodeoxynucleotides (ODNs) had been employed in gene modification and represent an alternative approach to 'cure' genetic disorders caused by mutations. To test the ability of ODN-mediated gene repair in bone marrow-derived mesenchymal stem cells (MSCs), we established MSCs cell lines with stably integrated mutant neomycin resistance and enhanced green fluorescent protein reporter genes. The established cultures showed morphologically homogenous population with phenotypic and functional features of mesenchymal progenitors. Transfection with gene-specific ODNs successfully repaired targeted cells resulting in the expression of functional proteins at relatively high frequency approaching 0.2%. Direct DNA sequencing confirmed that phenotype change resulted from the designated nucleotide correction at the target site. The position of the mismatchforming nucleotide was shown to be important structural feature for ODN repair activity. The genetically corrected MSCs were healthy and maintained an undifferentiated state. Furthermore, the genetically modified MSCs were able to engraft into many tissues of unconditioned transgenic mice making them an attractive therapeutic tool in a wide range of clinical applications.

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How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers?

Borrajo

Vidal

Alonso

et al. 2014

Polymers in Regenerative Medicine

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Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes

Cited by 211 publications

References 39 publications

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells

How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers?

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