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STROMAL CELL DERIVED FACTOR (SDF)-1 WITH BMP-2 AND TGF≤-B1 INDUCES SITE DIRECTED CELL HOMING, OSTEOGENIC AND CHONDROGENIC DIFFERENTIATION WITHOUT THE REQUIREMENT FOR CELL SEEDING
Presenter: Harvey Chim, MD
Co-Authors: Miller E; Gliniak C; Alsberg E
Case Western Reserve University

Background: Current tissue engineering approaches are limited by the requirement for a source of seeded cells, with attendant problems of donor site morbidity. We previously described the use of a new approach to tissue engineering, termed cell guidance , to induce homing of cells into scaffolds through creating a biomimetic environment by constant delivery of cytokines. In this study, we investigate the efficacy of this approach for bone and cartilage tissue engineering.

Methods: A cytokine microdelivery apparatus consisting of an implantable osmotic pump and microneedle system was used to deliver various combinations of stromal-cell derived factor (SDF)-1, bone morphogenic protein (BMP)-2 and transforming growth factor (TGF≤)-B1 at a constant rate to polyglycolic acid (PGA) scaffolds implanted intraperitoneally in rats. Groups were as follows: (1) SDF-1 (2) BMP-2 (3) TGF≤-B1 (4) SDF-1 & BMP-2 (5) SDF-1 & TGF≤-B1 (6) No cytokines. Animals were sacrificed after 1 month and specimens explanted for staining with Massons trichrome and Safranin O.

Results: Migration of cells into the scaffold was seen for groups 1 to 5, but not in group 6. SDF-1 with BMP-2 induced formation of osteoid throughout the scaffold, with a lesser extent of osteoid formation seen with only BMP-2. Early chondrogenesis was seen in scaffolds treated with SDF-1 and TGF≤-B1, with a decreased extent of chondrogenesis seen with only TGF≤-B1.

Conclusions: These results suggest that SDF-1 in combination with a differentiating cytokine is effective in inducing osteogenesis and chondrogenesis in vivo, without the requirement for prior cell seeding. Our findings support the use of cell guidance as a new approach for musculoskeletal tissue engineering. Studies in larger animals are needed to further research into this technique.


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