Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growt
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RESEARCH
Open Access
Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem cells Qian Wen, Chaoying Zhou, Wei Luo, Mingqian Zhou and Li Ma*
Abstract Background: Autologous transplantation of modified mesenchymal stem cells (MSCs) is a promising candidate for the treatment of the refractory clinical disease, avascular necrosis of the femoral head (ANFH). Our previous attempts by compounding MSCs with medical fibrin glue to treat ANFH in animal model have achieved excellent effects. However, the underlying molecular mechanism is unclear, especially on the transgenic gene expression. Methods: Rabbit MSCs were isolated and compounded with fibrin glue. Following degrading of fibrin glue, proliferation, viability, expression of transgenic hepatocyte growth factor gene as well as osteogenic differentiation of MSCs were evaluated together with that of uncompounded MSCs. Fibrin glue-compounded MSCs were transplanted into the lesion of ANFH model, and the therapeutic efficacy was compared with uncompounded MSCs. One-Way ANOVA was used to determine the statistical significance among treatment groups. Results: Fibrin glue compounding will not affect molecular activities of MSCs, including hepatocyte growth factor (HGF) secretion, cell proliferation and viability, and osteogenic differentiation in vitro. When applying fibrin glue-compounded MSCs for the therapy of ANFH in vivo, fibrin glue functioned as a drug delivery system and provided a sustaining microenvironment for MSCs which helped the relatively long-term secretion of HGF in the femoral head lesion and resulted in improved therapeutic efficacy when compared with uncompounded MSCs as indicated by hematoxylin-eosin staining and immunohistochemistry of osteocalcin, CD105 and HGF. Conclusion: Transplantation of fibrin glue-compounding MSCs is a promising novel method for ANFH therapy. Keywords: Avascular necrosis of the femoral head, Mesenchymal stem cell, Fibrin glue, Proliferation, Differentiation, Osteogenic regeneration
Background As an irreversibly progressive pathological process, avascular necrosis of the femoral head (ANFH) is regarded as an immortal and incurable disease which mainly afflicts people under 40-year-old [1-3]. Mesenchymal stem cells (MSCs)-based treatments are believed to be a promising method for ANFH therapy due to the osteogenic potential of MSCs and the convenience of preparation [4], and have been applied for therapy of ischemic * Correspondence: [email protected] Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, Guangdong 510515, People’s Republic of China
diseases such as ANFH [5-7] and myocardial infarction [8,9] with satisfactory effects. Medical fibrin glue is a biopolymer matrix composed by human natural fibrinogen and thrombin. Fibrin glue is commonly used for surgical hemostasis and tissue sealing as a sealant [10-12]. In recent years it has been applied
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