201. Stem cell-conditioned medium accelerates distraction osteogenesis through multiple regenerative mechanisms.
- Author
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Ando, Yuji, Matsubara, Kohki, Ishikawa, Jun, Fujio, Masahito, Shohara, Ryutaro, Hibi, Hideharu, Ueda, Minoru, and Yamamoto, Akihito
- Subjects
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STEM cells , *BONE growth , *LABORATORY mice , *CALLUS , *MESENCHYMAL stem cells , *ENDOTHELIAL cells , *PROGENITOR cells , *INFLAMMATION , *APOPTOSIS - Abstract
Abstract: Distraction osteogenesis (DO) successfully induces large-scale skeletal tissue regeneration, but it involves an undesirably long treatment period. A high-speed DO mouse model (H-DO) with a distraction speed twice that of a control DO model failed to generate new bone callus in the distraction gap. Here we demonstrate that the local administration of serum-free conditioned medium from human mesenchymal stem cells (MSC-CM) accelerated callus formation in the mouse H-DO model. Secretomic analysis identified factors contained in MSC-CM that recruit murine bone marrow stromal cells (mBMSCs) and endothelial cells/endothelial progenitor cells (EC/EPCs), inhibit inflammation and apoptosis, and promote osteoblast differentiation, angiogenesis, and cell proliferation. Functional assays identified MCP-1/-3 and IL-3/-6 as essential factors in recruiting mBMSCs and EC/EPCs. IL-3/-6 also enhanced the osteogenic differentiation of mBMSCs. MSC-CM that had been depleted of MCP-1/-3 failed to recruit mBMSCs, and consequently failed to promote callus formation. Taken together, our data suggest that MSCs produce a broad repertoire of trophic factors with tissue-regenerative activities that accelerate healing in the DO process. [Copyright &y& Elsevier]
- Published
- 2014
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