Bone Substitute Effect on Vascularization and Bone Remodeling after Application of phVEGF165 Transfected BMSC

Abstract

VEGF (vascular endothelial growth factor) promotes vascularization and remodeling of bone substitutes. The aim of this study was to examine the effect of distinct resorbable ceramic carriers on bone forming capacities of VEGF transfected bone marrow stromal cells (BMSC). A critical size defect of the radius in rabbits was filled either by a low surface scaffold called beta-TCP (tricalciumphsphate) or the high surface scaffold CDHA (calcium deficient hydroxy-apatite) loaded with autologous BMSC, which were either transfected with a control plasmid or a plasmid coding for phVEGF165. They were compared to unloaded scaffolds. Thus, six treatment groups (n = 6 in each group) were followed by X-ray over 16 weeks. After probe retrieval, the volume of new bone was measured by micro-CT scans and vascularization was assessed in histology. While only minor bone formation was found in both carriers when implanted alone, BMSC led to increased osteogenesis in both carriers. VEGF promoted vascularization of the scaffolds significantly in contrast to BMSC alone. Bone formation was increased in the beta-TCP group, whereas it was inhibited in the CDHA group that showed faster scaffold degradation. The results indicate that the interaction of VEGF transfected BMSC with resorbable ceramic carrier influences the ability to promote bone healing.

Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management

“…Indeed, its porous structure plays a role in its osteoconductive characteristics. 104 β -TCP gradually resorbs, and although its resorption is unpredictable 105 and slower than the resorption of calcium sulfate, 39 , 106 β -TCP is meant to be completely resorbed in time 58 , 100 , 107 by osteoclasts. 108 β -TCP resorbs in approximately 13–20 weeks after implantation and is then completely replaced by remodeled bone.…”

“… 8 , 9 , 23 , 94 , 113 , 114 Synthetic HA can be made by the precipitation of calcium nitrate and ammonium dihydrogen phosphate. 23 This association presents all the advantages of its two components (osteoconductivity, 94 , 115 – 118 biocompatibility, 94 , 113 safe and nonallergen use, 113 and promotion of bone formation 106 ). The major gain of using biphasic ceramics (HA and β-TCP mixture) concerns their resorption.…”

Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue – a review

“…IHC markers (factor VIII, CD31, CD34, CD105, VEGF and its receptors, etc.) are often used to establish microvessel density (MVD) [ 54 – 64 ]. This parameter is often presented as a number of microvessels per square millimeter or mean value with standard deviations.…”

“…Results in studies using this method in most cases are presented as mean values of positively stained cells (and/or structures) among counted experimental groups with their standard deviations [ 51 – 64 ]. If the IHC marker has a high affinity to cells, then the process of positive cells counting may be optimized by some special methods [ 69 ].…”

Therapeutic Effects of VEGF Gene-Transfected BMSCs Transplantation on Thin Endometrium in the Rat Model

“…There are many experimental studies showing the beneficial effects of VEGF gene-transfected stem cells transplantation on many disorders, such as bone defects, stroke, myocardial infarction, acute kidney injury, and bronchopulmonary dysplasia. [ 22 – 25 ].…”