In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7

Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

“…Similar results were reported in rats (r) where the bone volume measured by µ-Computed Tomography (µCT) within the pores of scaffold was over 100 fold higher with rBM-MSC (6.85mm³ ± 1.89) than with rAd-MSC (0.05 mm³ ± 0.05) 6 weeks after implantation; this was further confirmed by histology [54] . The Ad-MSC literature however shows that a preinduction or a pre-differentiation step would be required for Ad-MSC to promote bone formation [87][88][89][90] . This would therefore suggest a lower intrinsic bone forming capacity of Ad-MSC compared to BM-MSC.…”

Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

“…The transduced ASC and MSC embedded in fibrin gel both formed bone when implanted in the calvarial defect with no significant differences between the groups, though the ASC deposited a higher amount of calcified matrix. 145 Similarly, gene therapy approaches using ASC transduced to express BMP-7 derived from rats 146 and humans 147 have shown evidence for enhanced bone formation in vitro and in vivo. The BMP-7 was encased in a collagen I gel and implanted subcutaneously into rats 146 or SCID mice, 147 respectively, and caused an increase in mineralization, alkaline phosphatase activity, and osteocalcin expression.…”

“…145 Similarly, gene therapy approaches using ASC transduced to express BMP-7 derived from rats 146 and humans 147 have shown evidence for enhanced bone formation in vitro and in vivo. The BMP-7 was encased in a collagen I gel and implanted subcutaneously into rats 146 or SCID mice, 147 respectively, and caused an increase in mineralization, alkaline phosphatase activity, and osteocalcin expression. 146,147 Taken together, these transduction results are consistent with an in vitro study by Dragoo et al showing increased frequency of a BMP-2-transduced ASC-derived osteoblastic phenotype comparable to exogenous BMP-2 stimulation.…”

Skeletal and Adipose Tissue Engineering with Adipose-Derived Stromal Cells

“…A randomized clinical trial compared the use of BMP-7 versus autogenous bone graft in the treatment of tibial nonunions (Friedlaender, 2004) and found that using BMP-7 was equivalent in clinical outcomes without the morbidity of using an autogenous bone graft. Specifically with adipose-derived stromal cells, researchers using an adenovirus vector ex vivo to induce BMP-7 expression showed increased bone formation both in vitro and in vivo using rat adipose-derived stromal cells (Yang, et al 2005) and in human adipose-derived stromal cells (Kang Y, et al 2007). The fibroblast growth factor family has over twenty members and four receptors involved in diverse cellular processes from angiogenesis to wound healing.…”