Novel Bone Regenerative Medicine Using the Secretomes From Bone Marrow-derived Mesenchymal Stem Cells

Objectives: For bone regeneration, proliferative ability and multipotency of mesenchymal stem cells (MSCs) are worthwhile, however, spread of the bone regenerative therapy with MSCs are still restrictive because of the problems in safety, regulations and cost in handling cells. Furthermore, the mechanisms of transplanted cells are not fully recognized. Recently, it has been established that implanted MSCs secrete a variety of growth factors, and the paracrine effects of these secretomes may promote tissue repair. Conditioned media from MSCs (MSC-CM) includes several kinds of secretomes. The aim of this study is to understand the potential ability and mechanism of MSC-CM for bore regeneration.
Methods: All animal experiments were performed in accordance with the protocols approved by the institutional guidelines for animal experimentation. We used the commercially available human MSCs and they were cultured and MSC-CM was obtained from their serum-free conditioned media. The growth factors in MSC-CM were quantified. Rat MSCs (rMSCs) were cultured with MSC-CM and the ability of migration and tube formation as well as the expression of osteogenic and angiogenic related-genes of rMSCs were examined. In vivo, MSC-CM was transplanted into rats’ calvarial bone defects with collagen sponges. Migration of stem cells, bone regeneration and angiogenesis were evaluated by histologically, immunohistochemically and radiographically.
Results: MSC-CM included several growth factors such as insulin like growth factor (IGF)-1, transforming growth factor (TGF)β-1 and vascular endothelial growth factor (VEGF)-1. MSC-CM enhanced the migration of stem cells, tube formation and the expression of some osteogenic and angiogenic related-genes in vitro. In vivo, the early bone regeneration and angiogenesis were confirmed compared with the control groups.
Conclusions: Our results show that MSC-CM promotes angiogenesis and bone regeneration via multifaceted paracrine mechanisms by its secretomes and it may provide significant therapeutic benefits instead of transplantation of MSCs or existing agents.