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 Â 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 b-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. ß

Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells

“…Type II collagenase (Shanghai Yuanju Bio-Tech Co., Ltd., Shanghai, China) was used for enzymatic digestion to achieve a single-cell suspension from the penile corpora cavernosa tissue. Then, density gradient centrifugation and the preplate technique based on differential adhesion were used, and adherent cells preplate 1 [PP1] were acquired, followed by repeated preplating procedures, until preplate 6 (PP6) cells were acquired Nishimori et al 2012;Nolazco et al 2008), then we confirmed that the PP6 cells were primarily composed of MDSCs.…”

Juxtacrine and Paracrine Interactions of Rat Marrow-Derived Mesenchymal Stem Cells, Muscle-Derived Satellite Cells, and Neonatal Cardiomyocytes with Endothelial Cells in Angiogenesis Dynamics

“…Other progenitors such as muscle-resident stem cells, known as satellite cells (SCs), are capable of producing a number of angiogenic growth factors. SC transplantation in experimentally injured mouse medial collateral ligament was reported to have accelerated angiogenesis and increased capillary density [8]. Moreover, in the coculture of rat SCs and microvascular fragments, the index of angiogenesis is greater than that of single culture alone [9].…”

“…The stimulatory effect of the stem cell-derived CM on endothelial tube-like formation in vitro and arteriolar development in vivo confirmed the importance of paracrine signaling. It has been reported that a number of angiogenic inducers, including FGF, VEGF, IGF, and HGF, are produced by SCs [8]. Also, selected members of metalloproteases and extracellular matrix-degrading enzymes are secreted by human muscle SCs, which may participate in remodeling and in myogenesis [41].…”

Platelet-rich plasma did not improve early healing of medial collateral ligament in rats

“…Load was applied along the longitudinal axis of the MCL, 100 N load cell was used. A pre-load of 0.1 N was applied to the ligament and the MCL was preconditioned (cyclically loaded to approximately 1 % strain for 10 cycles).After preconditioning, each femur-MCL-tibia complex was stretched at a cross-head speed of 0.25 mm/s until gross failure of the MCL occurred [17]. The load/ displacement readings were taken from the material testing machine output.…”