title: Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament.
abstract: We performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC-VEGF), (2) soluble fms-like tyrosine kinase-1 (sFLT1, a VEGF-specific antagonist) and nLacZ (MDSC-sFLT1), and (3) nLacZ (MDSC-nLacZ). After transecting the MCL of immunodeficient rats, 5 × 10(5)  cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate-buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and β-galactosidase double positive cells in the rats transplanted with MDSC-VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC-VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC-VEGF and MDSC-nLacZ groups. On the other hand, the MDSC-sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC-sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL.
authors.affiliation: Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh, Bridgeside Point 2, 450 Technology Drive, Pittsburgh, Pennsylvania 15219, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishimori
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shusuke
authors.initials: S
authors.lastname: Ota
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kopf
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mifune
authors.forename: Christopher
authors.initials: C
authors.lastname: Harner
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007718:Knee Injuries / Q000503:physiopathology / Q000628:therapy*; D007763:Lac Operon; D017888:Medial Collateral Ligament, Knee / Q000098:blood supply / Q000166:cytology / Q000293:injuries; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011923:Rats, Nude; D020127:Recovery of Function / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C467498:vascular endothelial growth factor A, rat; C501163:Flt1 protein, mouse; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1