遺伝子治療 :組み換えアデノウイルスベクターによりBMP2遺伝子を導入した間葉系幹細胞移植による骨再生
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キーワード:アデノウイルス、間葉系幹細胞、同種異系移植、骨形成、遺伝子治療 The stromal elements of bone marrow include cells, referred to as mesenchymal stem cells (MSCs), that have the potential to differentiate into osteoblasts, chondrocytes, myocytes, adipocytes and fibroblasts. It has been well established that bone morph-ogenic protein 2 (BMP2) can induce orthotopic and ectopic bone formation. A possible approach to producing bone in vivo involves the use of gene therapy in which viral vectors are utilized to introduce the BMP2 gene into MSC. We reported that the introduction of recombinant adenovirus-mediated human BMP2 gene enabled MSC to produce BMP2 protein, to be differentiated into an osteoprogenitor line, and to induce bone formation in vitro. Regarding age and the osteogenic potential of MSC, we exhibited that the proliferation and osteogenic differentiation potential of MSCs from aged human was maintained. Our previous studies showed that MSCs engineered with the gene for BMP2 were capable of inducing autologous bone formation in several animal models. Moreover, we investigated whether allogeneic BMP2-engineered MSC would facilitate bone healing using rats with a femoral segment defect model. Engineered MSC completely repaired the bone defect. Abundant structual bone and well-developed cortical bone was noted by 8 weeks after transplantation. We also demonstrated that allogeneic BMP2-engineered MSC not only act as a gene deliverer, but also are directly involved in bone repair. Key words : Adenovirus, Mesenchymal stem cells, allogeneic transplantation, bone formation, gene therapy
- 山形大学の論文
- 2004-02-16