Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding.
The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient's own cells to an implanted scaffold through controlled delivery of cytokines. In this study, we used stromal-cell-derived factor 1-alpha (SDF-1α) in combination with bone morphogenic protein (BMP)-2 or transforming growth factor (TGF)-β1 to induce cell migration and osteogenic or chondrogenic differentiation, respectively, in implanted scaffolds in a rat model. A customized cytokine microdelivery apparatus was used to ensure the constant rate and concentration of cytokine delivery around the scaffold. The formation of osteoid or early cartilage was observed after 4 weeks in specimens treated with SDF-1α and either BMP-2 or TGF-β1. The density of cellular infiltrate and formation of differentiated tissue were lower in scaffolds treated only with BMP-2 or TGF-β1. Thus, controlled SDF-1α delivery induces cell migration into scaffolds and can result in enhanced osteogenesis and chondrogenesis when used in combination with differentiation cytokines for purposes of tissue engineering.
Department of Plastic Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA. harveychim@yahoo.com
Harvey
H
Chim
Erin
E
Miller
Christy
C
Gliniak
Eben
E
Alsberg
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D020219:Chondrogenesis / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D053773:Transforming Growth Factor beta1