RESUMEN
In this study, the effects of ginsenoside Rg1, a natural compound isolated from Panax ginseng, on human umbilical vein endothelial cell (HUVEC) behavior in vitro, and on angiogenesis and tissue regeneration in genipin-fixed acellular tissue (extracellular matrix, ECM) in vivo, were investigated. Basic fibroblast growth factor (bFGF) was used as a control. The in vitro results indicated that in the presence of bFGF or Rg1, HUVEC proliferation was significantly increased. Both bFGF and Rg1 promoted HUVEC migration in a Transwell plate assay. In addition, bFGF or Rg1 significantly increased the formation of capillary-like network by HUVECs on Matrigel. Thus, both bFGF and Rg1 enhanced multiple components of angiogenic activity in vitro. The in vivo results obtained 1 week postoperatively showed that the extent of angiogenesis in ECMs was significantly enhanced by bFGF or Rg1. At 1 month postoperatively, vascularized neoconnective tissues were found to fill the pores within ECMs loaded with bFGF or Rg1. There was a significant increase in neocapillary density from 1 week to 1 month for ECMs loaded with Rg1, whereas that observed in ECMs loaded with bFGF stayed approximately the same because of the limitations of protein stability. These results suggested that Rg1 may be a new class of angiogenic agent and may be loaded in ECMs to accelerate tissue regeneration.
Asunto(s)
Inductores de la Angiogénesis/farmacología , Células Endoteliales/efectos de los fármacos , Ginsenósidos/farmacología , Ingeniería de Tejidos , Animales , Rastreo Diferencial de Calorimetría , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Matriz Extracelular , Calor , Humanos , Masculino , Panax , Ratas , Ratas WistarRESUMEN
PURPOSE: The primary challenge for tissue engineering is to develop a vascular supply that can support the metabolic needs of the engineered tissues in an extracellular matrix. In this study, the feasibility of using a natural compound, ginsenoside Re, isolated from Panax ginseng in stimulating angiogenesis and for tissue regeneration was evaluated. METHODS: Effects of ginsenoside Re on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were examined in vitro. Additionally, angiogenesis and tissue regeneration in a genipin-fixed porous acellular bovine pericardium (extracellular matrix; ECM) incorporated with ginsenoside Re implanted subcutaneously in a rat model were investigated. Basic fibroblast growth factor (bFGF) was used as a control. RESULTS: It was found that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF or ginsenoside Re. Additionally, effects of ginsenoside Re on HUVEC proliferation, migration, and tube formation were dose-dependent and reached a maximal level at a concentration of about 30 microg/ml. The in vivo results obtained at 1 week postoperatively showed that the density of neocapillaries and the tissue hemoglobin content in the ECMs were significantly enhanced by bFGF or ginsenoside Re. These results indicated that angiogenesis in the ECMs was significantly enhanced by loading with bFGF or ginsenoside Re. At 1 month postoperatively, vascularzied neo-connective-tissue fibrils were found to fill the pores in the ECMs loaded with bFGF or ginsenoside Re. CONCLUSIONS: The aforementioned results indicated that like bFGF, ginsenoside Re-associated induction of angiogenesis enhanced tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.