Original Article
Gene Therapy (2008) 15, 1523–1535; doi:10.1038/gt.2008.110; published online 17 July 2008
Treatment of avascular necrosis of the femoral head by hepatocyte growth factor-transgenic bone marrow stromal stem cells
Q Wen1, L Ma1, Y-P Chen2, L Yang2, W Luo1 and X-N Wang3
- 1Institute of Molecular Immunology, Southern Medical University, Guangzhou, People's Republic of China
- 2Department of Imageology, Nanfang Hospital, Guangzhou, People's Republic of China
- 3School of Biosciences and Bioengineering, South China University of Technology, Guangzhou, People's Republic of China
Correspondence: Professor L Ma, Institute of Molecular Immunology, Southern Medical University, No. 1838, Northern Guangzhou Avenue, Guangzhou, Guangdong, 510515, People's Republic of China. E-mail: maryhmz@126.com; X-N Wang, School of Biosciences and Bioengineering, South China University of Technology, Guangzhou, Guangdong, 510641, People's Republic of China. E-mail: xnwang@21cn.net.
Received 14 January 2008; Revised 14 May 2008; Accepted 16 May 2008; Published online 17 July 2008.
Abstract
The treatment of hormone-induced early-stage avascular necrosis of the femoral head (ANFH) with transplantation of hepatocyte growth factor (HGF)-transgenic bone marrow stromal stem cells (BMSCs) was examined. A rabbit model of hormone-induced early ANFH was first established. BMSCs were transplanted by core decompression under the guidance of computed tomography (CT). A supportive fibrinogen drug delivery mixture (FG) was tested for mechanical enhancement of stem cell delivery. Therapeutic efficacy was evaluated by CT, magnetic resonance imaging (MRI), CT perfusion imaging, ink artery infusion angiography, hematoxylin-and-eosin staining and immunohistochemical staining for extracellular signal-regulated kinase-1/2 of pathological sections. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving transplanted transgenic BMSCs with FG. Newly generated capillaries were visible on the bone plates of the trabeculae, and the bone marrow was rich in hematopoietic tissue. These results demonstrate that the combination of core decompression and transplantation of HGF transgenic autologous BMSCs enhanced blood vessel regeneration and bone reconstruction in the ANFH model. This study provides experimental data that motivate possible clinical use of this therapeutic strategy.
Keywords:
avascular necrosis of the femoral head, hepatocyte growth factor, bone marrow stromal stem cells, fibrin glue
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