The Effect of Regional Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone-Marrow Cells on the Repair of Segmental Femoral Defects in Rats*

Ex vivo gene therapy with stromal cells transduced with a retroviral vector containing the BMP4 gene completely heals critical size calvarial defect in rats

“…Although there are several studies which have shown evidence for skeletal regeneration in vivo using ex vivo modified stromal cells, myoblasts, or fibroblasts, 10,15,16,22,24,25 our study is unique in that it provides quantitative data on the extent of healing by valid bone density measurements. Furthermore, our data demonstrate that the healing of a critical calvarial defect is dependent on the time of exposure, as well as the number of BMP4-expressing stromal cells implanted.…”

“…[9][10][11][12][13][14] Accordingly, it has been shown that adenoviral transfer of BMP2 can stimulate bone formation at ectopic sites 16 and promote healing of a segmental defect in long bones. 9,14 In as much as the results of previous work using adenoviral vectors are promising and adenoviral vector systems have the advantage of high levels of gene expression acutely, adenoviral vector systems also have two important disadvantages: (1) these vectors, even with the use of 'gutted' adenoviral vectors, frequently elicit strong immune response, which is highly undesirable.…”

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

“…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).…”

Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits

“…However, harvesting autogenous bone graft is inevitably associated with donor site morbidities and increased surgical time [27]. Therefore, extensive basic and clinical researches have been directed at developing alternatives to autogenous bone graft [11,15,17,18,21,26].…”