title: Transplanted blood-derived endothelial progenitor cells (EPC) enhance bridging of sheep tibia critical size defects.
abstract: The angiogenic events that accompany bone regeneration function as a "limiting factor" and are the primary regulatory mechanisms that direct the healing process. The general aim of this study was to test whether blood-derived progenitor cells that have endothelial characteristics (EPC), when applied to a large segmental defect, would promote bone regeneration. We established a critical-sized gap platform in sheep tibiae. Our model system takes advantage of the physiological wound healing process that occurs during the first two weeks following injury, and results in the gap being filled with scar tissue. EPC were expanded ex-vivo and 2 x 10(7) cells/0.2 ml were implanted into a wedged-shaped canal excavated in the fibrotic scar tissue. Sham treated sheep served as controls. Bone regeneration was followed every two weeks for three months by X-ray radiography. At the end of the experimental period, the regenerating segments were subjected to micro-computed tomographic (microCT) analysis. While minimal bone formation was detected in sham-treated sheep, six out of seven autologous EPC-transplanted sheep showed initial mineralization already by 2 weeks and complete bridging by 8-12 weeks post EPC transplantation. Histology of gaps 12 weeks post sham treatment showed mostly fibrotic scar tissue. On the contrary, EPC transplantation led to formation of dense and massive woven bone all throughout the defect. The results of this preclinical study open new therapeutic opportunities for the treatment of large scale bone injuries.
authors: Department of Orthopaedic Surgery, Ha'emek Medical Center, Afula 18101, Israel.
authors: Nimrod
authors: N
authors: Rozen
authors: Tova
authors: T
authors: Bick
authors: Alon
authors: A
authors: Bajayo
authors: Ben
authors: B
authors: Shamian
authors: Michal
authors: M
authors: Schrift-Tzadok
authors: Yankel
authors: Y
authors: Gabet
authors: Avner
authors: A
authors: Yayon
authors: Itai
authors: I
authors: Bab
authors: Michael
authors: M
authors: Soudry
authors: Dina
authors: D
authors: Lewinson
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D012756:Sheep; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology*; D055114:X-Ray Microtomography