Role of FGF-2 on human bone marrow stem cells-induced collagen tissue regeneration

Abstract

Role of FGF-2 on Human Bone Marrow Stem Cells-induced Collagen Tissue RegenerationObjectives: Role of Bone Marrow Stem Cells (BMSCs) on collagen tissue regeneration, which is essential for wound healing process, might be modified by various biologic stimuli. The aim of this study was to assess the effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human BMSCs (hBMSCs) in vitro and in vivo.Materials and Methods: hBMSCs were isolated from human vertebral bone marrow during a vertebral surgery. To confirm the stem cell population in the isolated cell group, characterization of cells used in this study was performed using well established in vitro and in vivo assay models. The effect of FGF-2 (0, 2, 5, 20 ng/ml) treatment on biologic changes of characterization of hBMSCs was analyzed thoroughly. In order to investigate the effect of FGF-2 on the hBMSCs induced collagen tissue regeneration, in vitro insoluble/soluble collagen and corresponding hydroxyproline synthesis were assessed and real-time polymerase chain reaction (PCR) was performed using types of collagen and Lox (Lysyl oxidase) family genes. In vivo collagen formation was examined after hBMSCs were transplanted using an in vivo assay model for collagen tissue regeneration. After 8 weeks of healing, histologic and immunohistochemistry analysis were performed (n = 4).Results: hBMSCs population with the characteristics of MSCs (Mesenchymal Stem Cells) was present in isolated cells from bone marrow of human vertebrae. Effect of FGF-2 on hBMSCs showed results consistent with previous reports in terms of CFE (Colony Forming Efficiency), proliferation, and in vitro differentiation. The amount of insoluble/soluble collagen production was also significantly enhanced in hBMSCs expanded with FGF-2 compared to hBMSCs without FGF-2. Although the changes of expression pattern of collagen-related mRNA were different dependent on the type of specific gene, FGF-2 decreased collagen type I expression of hBMSCs while it increased collagen type III. Expression of all Lox family gene was enhanced following FGF-2 treatment. The histologic and immunohistochemistry results revealed that the collagen formed in vivo by hBMSCs showed more relevant amount and well-organized structure in the FGF-2 treated hBMSCs at 8 weeks (p< 0.05)Conclusion: FGF-2 facilitates the properties and collagen producing potency of hBMSCs, rendering them more suitable for collagen regeneration mediated wound healing by hBMSCs.