A Natural Compound (Ginsenoside Re) Isolated from Panax ginseng as a Novel Angiogenic Agent for Tissue Regeneration
- 366 Downloads
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.
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.
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 μg/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.
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.
Key words:acellular tissue angiogenic agent ginsenoside Re tissue regeneration
basic fibroblast growth factor
the ECM loaded with bFGF
the ECM dip-coated in the drug-free gelatin solution
the ECM loaded with ginsenoside Re
hematoxylin and eosin
human umbilical vein endothelial cell
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
nitric oxide synthase
phosphate buffered saline
Unable to display preview. Download preview PDF.
- 6.6. K. Y. Lee, C. R. Halberstadt, W. D. Holder, and D. J. Mooney. Breast reconstruction, In: R. P. Lanza, R. Langer, and J. Vacanti, (eds), Principles of Tissue Engineering. Academic Press, New York, 2000, pp. 409–423Google Scholar
- 14.14. S. Babaei and D. J. Stewart. Overexpression of endothelial NO synthase induces angiogenesis in a co-culture model. Cardiovas. Res. 55:190–200 (2002).Google Scholar
- 16.16. K. A. Hotchkiss, A. W. Ashton, R. Mahmood, R. G. Russell, J. A. Sparano, and E. L. Schwartz. Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. Mol. Cancer Ther. 1:1191–1200 (2002).PubMedGoogle Scholar
- 21.21. O. H. Lee, Y. M. Kim, Y. M. Lee, E. J. Moon, D. J. Lee, J. H. Kim, K. W. Kim, and Y. G. Kwon. Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 264:743–750 (1999).PubMedGoogle Scholar
- 29.29. S. J. Bryant and K. S. Anseth. Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage. J. Biomed. Mater. Res. 64A:70–79 (2003).Google Scholar
- 30.30. A. Bader, T. Schiling, and O. E. Teebken. Tissue engineering of heart valves-human endothelial cell seeding of detergent acellularized porcine valves. Euro. J. Cardio. Thoracic. Sur. 14:279–284 (1998).Google Scholar
- 31.31. Y. Tabata, M. Miyao, M. Yamamoto, and Y. Ikada. Vascularization into a porous sponge by sustained release of basic fibroblast growth factor. J. Biomater. Sci. Polymer Edn. 10:957–968 (1999).Google Scholar
- 32.32. F. Esch, A. Baird, N. Ling, N. Ueno, F. Hill, L. Denoroy, R. Klepper, D. Gospodarowicz, P. Bohlen, and R. Guillemin. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc. Natl. Acad. Sci. USA 82:6507–6511 (1985).PubMedGoogle Scholar
- 41.41. S. Fujikawa, T. Yokota, K. Koga, and J. Kumada. The continuous hydrolysis of geniposide to genipin using immobilized β-glucosidase on calcium alginate gel. Biotechnol. Lett. 9:697–702 (1987).Google Scholar
- 42.42. T. H. Tsai, J. Westly, T. F. Lee, and C. F. Chen. Identification and determination of geniposide, genipin, gardenoside, and geniposidic acid from herbs by HPLC/photodiode-array detection. J. Liq. Chromatogr. 17:2199–2205 (1944).Google Scholar
- 46.46. A. Perets, Y. Baruch, F. Weisbuch, G. Shoshany, G. Neufeld, and S. Cohen. Enhancing the vascularization of three-dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres. J. Biomed. Mater. Res. 65A:489–497 (2003).Google Scholar