Epiphysiodesis with infusion of stromal cell-derived factor-1 in rabbit growth plates

• Published in: Journal of bone and joint surgery. American volume 2007, Vol.89A (1), p.102-113
• Main Authors: LEE, Mark C, BIER, Adam D, NICKISCH, Florian, EBERSON, Craig P, EHRLICH, Michael G, QIAN CHEN
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Development - drug effects; Cartilage, Articular - anatomy & histology; Chemokine CXCL12; Chemokines, CXC - administration & dosage; Chemokines, CXC - pharmacology; Diseases of the osteoarticular system; Epiphyses - drug effects; Epiphyses - growth & development; Epiphyses - pathology; Indicators and Reagents; Infusion Pumps; Medical sciences; Methylene Blue; Miscellaneous. Osteoarticular involvement in other diseases; Orthopedic surgery; Rabbits; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tibia - drug effects; Tibia - growth & development
• ISSN: 0021-9355; 1535-1386
• DOI: 10.2106/00004623-200701000-00015

The mechanism of physeal closure is poorly understood, although both mechanical and biological factors may play a role in the process. In this study, we evaluated the effect of the application of a chemokine stromal cell-derived factor-1 (SDF-1) to rabbit physes in vivo with regard to growth inhibition. A continuous infusion system consisting of a fenestrated catheter and an osmotic pump were implanted into the right proximal tibial physis of twenty six-week-old New Zealand White rabbits. Ten of the pumps were loaded with human recombinant SDF-1alpha, and ten were loaded with phosphate-buffered saline solution (sham treatment). The left leg was used as the uninvolved control. The growth of the tibiae was followed radiographically for eight weeks, and histologic analysis was performed for both the SDF-1-treated rabbits and the sham-treated rabbits at two, four, and eight-week time-points. Radiographic evaluation showed a significant growth inhibition in the SDF-1alpha-treated physes (4.5 +/- 3.0 mm; p = 0.007) compared with the sham-treated physes after eight weeks. No difference was noted when the sham-treated leg was compared with the contralateral, control leg (0.2 +/- 2.9 mm; p = 0.465). Histologic evaluation showed marked physeal disorganization, narrowing, and proteoglycan loss and a significant decrease in physeal height (p < 0.0001) for the SDF-1-treated group. Reversible growth slowing was noted in the uninvolved, control leg of the SDF-1-treated group at six weeks, with resolution of the difference by eight weeks. SDF-1 may be used to induce physeal closure through a targeted infusion system. However, transient systemic effects of SDF-1 may exist and must be evaluated further prior to its clinical use for epiphysiodesis.