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Osteogenic priming of mesenchymal stem cells by chondrocyte-conditioned factors and mineralized matrix
- Osteogenic priming of mesenchymal stem cells by chondrocyte-conditioned factors and mineralized matrix
- Ro, Hyunuk; Park, Jungha; Yang, Kisuk; Kim, Jiyong; Yim, Hyun-Gu; Jung, Giyoung; Lee, Hyukjin; Cho, Seung-Woo; Hwang, Nathaniel S.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- CELL AND TISSUE RESEARCH
- 0302-766X; 1432-0878
- vol. 362, no. 1, pp. 115 - 126
- Osteogenic differentiation; Mineralized scaffolds; Simulated body fluids; Tissue engineering; Stem cells; Conditioned medium; In vivo implantation; Mouse (BALB/c)
- SCI; SCIE; SCOPUS
- Transient cartilage and a mineralizing microenvironment play pivotal roles in mesenchymal cell ossification during bone formation. In order to recreate these microenvironmental cues, C3H10T1/2 murine mesenchymal stem cells (MSCs) were exposed to chondrocyte-conditioned medium (CM) and seeded onto three-dimensional mineralized scaffolds for bone regeneration. Expansion of C3H10T1/2 cells with CM resulted in enhanced expression levels of chondrogenic markers such as aggrecan, type II collagen, type X collagen, and Sox9, rather than of osteogenic genes. Interestingly, CM expansion led to reduced expression levels of osteogenic genes such as alkaline phosphatase (ALP), type I collagen, osteocalcin, and Runx2. However, CM-expanded C3H10T1/2 cells showed enhanced osteogenic differentiation as indicated by increased ALP and Alizarin Red S staining upon osteogenic factor exposure. In vivo, CM-expanded C3H10T1/2 mesenchymal cells were seeded onto mineralized scaffolds (fabricated with polydopamine and coated with simulated body fluids) and implanted into critical-sized calvarial-defect mouse models. After 8 weeks of implantation, mouse skulls were collected, and bone tissue regeneration was evaluated by micro-computed tumography and Masson's trichrome staining. In accordance with the in vitro analysis, CM-expanded C3H10T1/2 cells gave enhanced bone mineral deposition. Thus, chondrocyte-conditioned factors and a mineralized microenvironment stimulate the bone formation of MSCs.
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