Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo

被引:155
作者
Rutherford, RB
Moalli, M
Franceschi, RT
Wang, D
Gu, K
Krebsbach, PH
机构
[1] Univ Michigan, Sch Dent, Ctr Biorestorat Oral Hlth, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Orthoped Surg, Ann Arbor, MI USA
来源
TISSUE ENGINEERING | 2002年 / 8卷 / 03期
关键词
D O I
10.1089/107632702760184709
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo. Here we show that BMP-7-transduced fibroblasts suspended in injectable thermoset hydrogels form complete ossicles on subcutaneous injection and repair segmental defects in rat femurs. Bone formation was preceded by an intermediate cartilage stage. To determine the fate of the implanted transduced cells, thermoset hydrogel suspensions of ex vivo BMP-7-transduced or nontransduced fibroblasts were placed in diffusion chambers and implanted to allow development in vivo without direct contact with host cells. Only the BMP-transduced fibroblasts formed bone within the diffusion chambers in vivo, revealing that BMP transduction induces osteoblastic conversion of these cells.
引用
收藏
页码:441 / 452
页数:12
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