Cell-secreted matrices perpetuate the bone-forming phenotype of differentiated mesenchymal stem cells
| Autor: | J. Kent Leach, Vaishali Mittal, Christopher A. Zikry, Debika Mitra, Allison I. Hoch, Nina L. Vollmer |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Materials science Stromal cell Cellular differentiation Biophysics Biomedical Engineering Bioengineering 02 engineering and technology Regenerative Medicine Article Biomaterials Extracellular matrix 03 medical and health sciences chemistry.chemical_compound Mice Osteogenesis Stem Cell Research - Nonembryonic - Human Animals Humans Bone Cell Proliferation Transplantation Decellularization Mesenchymal stem/stromal cells Bone Development 5.2 Cellular and gene therapies Cell growth Mesenchymal stem cell fungi Cell Differentiation Mesenchymal Stem Cells 021001 nanoscience & nanotechnology Stem Cell Research Cell biology Vascular endothelial growth factor 030104 developmental biology chemistry Mechanics of Materials Musculoskeletal Immunology Ceramics and Composites Stem Cell Research - Nonembryonic - Non-Human Dedifferentiation Development of treatments and therapeutic interventions 0210 nano-technology Rheology Biotechnology |
| Popis: | Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24h following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the invitro-acquired mineral-producing phenotype and accelerate the process of bone repair. |
| Databáze: | OpenAIRE |
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