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Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament
Author(s) -
Nishimori Makoto,
Matsumoto Tomoyuki,
Ota Shusuke,
Kopf Sebastian,
Mifune Yutaka,
Harner Christopher,
Ochi Mitsuo,
Fu Freddie H.,
Huard Johnny
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21551
Subject(s) - angiogenesis , medial collateral ligament , medicine , vascular endothelial growth factor , stem cell , immunohistochemistry , vegf receptors , pathology , immunology , cancer research , ligament , surgery , microbiology and biotechnology , biology
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. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:627–633, 2012