Comparison of Platelet-Rich Plasma and VEGF-Transfected Mesenchymal Stem Cells on Vascularization and Bone Formation in a Critical-Size Bone Defect

Abstract

Both platelet-rich plasma (PRP) and vascular endothelial growth factor (VEGF) can promote regeneration. The aim of this study was to compare the effects of these two elements on bone formation and vascularization in combination with bone marrow stromal cells (BMSC) in a critical-size bone defect in rabbits. The critical-size defects of the radius were filled with: (1) a calcium-deficient hydroxyapatite (CDHA) scaffold + phVEGF<sub>165</sub>-transfected BMSC (VEGF group), (2) CDHA and PRP, or (3) CDHA, autogenous BMSC, and PRP. As controls served: (4) the CDHA scaffold alone and (5) the CDHA scaffold and autogenous BMSC. The volume of new bone was measured by means of micro-CT scans, and vascularization was assessed in histology after 16 weeks. Bone formation was higher in the PRP + CDHA, BMSC + CDHA, and PRP + BMSC + CDHA groups than in the VEGF group (p < 0.05). VEGF transfection significantly promoted vascularization of the scaffolds in contrast to BMSC and PRP (p < 0.05), but was similar to the result of the CDHA + PRP + BMSC group. The results show that VEGF-transfected BMSC as well as the combination of PRP and BMSC improve vascularization, but bone healing was better with the combination of BMSC and PRP than with VEGF-transfected BMSC. Expression of VEGF in BMSC as a single growth factor does not seem to be as effective for bone formation as expanded BMSC alone or PRP which contains a mixture of growth factors.

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…Similar results were reported in the double Ang-1/BMP-2 and VEGF/BMP-2-overexpressing BM-MSCs [47, [116][117][118]. However, BM-MSCs engineered to exclusively overexpress the pro-angiogenic VEGF gene were found to be strong inducers of new bone formation by the promotion of new vessel formation among the scaffolds used as templates [119,120]. Curiously, BMMSCs were converted into bone tissue after the overexpression of the Epo gene [121].…”

“…GDF-5 [102][103][104] TIMP-1 [106] Bcl-2 [101] BONE FORMATION BMP-2 [86][109-111] BMP-2/SDF-1β [113] BMP-2/HIF-1α [114] BMP-2/Ang-1 [47] BMP-2/VEGF [116][117][118] BMP-2/miR-148b [142] BMP-4/-6/-7 [125,126] VEGF [119,120] Epo [121] IGF-I [128,129] OGP [127] Leptin [130] PDGF [131] ephrinB2 [132] ITGA2 [133] NELL1 [134] β-catenin [135] HI Cb TA Fo Na LIVER REGENERATION VEGF [144] ATP7B [155] HN HN…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Rabbit: [218] (bFGF-rbMPC), [149] (rbMPC/ferumoxide), [219] (hAng1-rbMPCs/PRP), [220] (hVEGF-rbMPC/PRP) Minipig: [221] (hBMP2/hVEGF-pADMPC), [222] (US2/US3-pADMPC)…”

Bone Marrow Aspirate Concentrate in Animal Long Bone Healing

“…Using the terms [(bmac OR bone marrow aspirate concentrate OR bmc OR bone marrow concentrate, OR mesenchymal stem cells) AND (bone OR osteogenesis OR fracture healing OR nonunion, OR delayed union)] we searched the PubMed/MEDLINE and the EMBASE electronic database in July [14][15][16][17][18][19][20][21][22][23][24][25]2014. The reference lists of included studies were also reviewed and compared with the collected studies to ensure no pertinent articles were omitted.…”

“…Eight studies (23%) reported cluster of differentiation (CD) markers. [17][18][19][20][21][22][23][24] Three studies (8%) analyzed for growth factors, which primarily focused on vascular endothelial growth factor (VEGF). 19,20,23 …”