Noggin improves bone healing elicited by muscle stem cells expressing inducible BMP4

被引:40
作者
Peng, HR
Usas, A
Hannallah, D
Olshanski, A
Cooper, GM
Huard, J
机构
[1] Univ Pittsburgh, Dept Orthopaed Surg, Rangos Res Ctr 4100, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA
[4] Childrens Hosp Pittsburgh, Growth & Dev Lab, Pittsburgh, PA 15213 USA
[5] Conemaugh Mem Med Ctr, Dept Surg, Johnstown, PA 15905 USA
关键词
Noggin; BMP4; inducible promoter; muscle stem cells; bone healing; calvarial defect;
D O I
10.1016/j.ymthe.2005.02.027
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The aim of this study was to test the hypothesis that a specific antagonist may enhance the efficacy of its corresponding growth factor in a regulated tissue engineering strategy. Our prior research has led to the development of a retroviral vector that enables optimal regulated bone morphogenetic protein 4 (BMP4) expression in vitro and regulated bone formation in vivo with transduced muscle stem cells. However, when implanted in critical-sized calvarial defects, these cells led to residual bone formation without induction or bone overgrowth with induction, even at reduced cell doses. We thus coimplanted the aforementioned cells with stem cells engineered to express Noggin, a specific BMP antagonist. This approach, while preserving our ability to regulate bone regeneration closely, prevented both the basal level bone regeneration and the bone overgrowth and, more importantly, led to the regeneration of bone that more closely resembled normal bone. We believe that this regulatable tissue engineering strategy, enhanced by utilizing a specific antagonist, constitutes a new paradigm for tissue engineering and regenerative medicine.
引用
收藏
页码:239 / 246
页数:8
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