Publications (18) View all
-
Article: Pigment epithelium-derived factor delays cellular senescence of human mesenchymal stem cells in vitro by reducing oxidative stress.
[show abstract] [hide abstract]
ABSTRACT: Mesenchymal stem cells (MSCs) are multipotent progenitor cells that represent a promising approach in the field of regenerative medicine; however, this potential diminishes with senescence. Pigment epithelium-derived factor (PEDF) gives some protection by reducing oxidative stress, which is known to accelerate cellular senescence. Thus we hypothesized that PEDF could delay senescence during MSC expansion by reducing oxidative stress. Proliferation and differentiation potentials, oxidative stress, senescence and p53/p16 expressions have been examined. In MSCs cultured under normoxic conditions treated with PEDF, proliferative lifespan in vitro was significantly increased compared with control group not given PEDF, with ∼10 additional population doublings (PD) occurring before terminal growth arrest. Most of the MSCs cultured under normoxic conditions ceased to proliferate after 20-28 PD, while few senescent cells were found in the hypoxic, PEDF-hypoxic and PEDF-normoxic cultures; this was associated with downregulation of p53 and p16 expression and decreased oxidative stress. PEDF also preserved differentiation potentials of MSCs compared with the control group. Thus PEDF suppression of oxidative stress delays cellular senescence and allows greater expansion of MSCs.Cell Biology International 01/2013; · 1.48 Impact Factor -
Article: Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.
[show abstract] [hide abstract]
ABSTRACT: Ghrelin has been reported to protect the cardiovascular system; however, the cardioprotective effect of ghrelin against cardiopulmonary bypass (CPB) induced myocardial injury are unclear. In this study, the protective effect of ghrelin on CPB induced myocardial injury and the underlying mechanisms were investigated. Adult male rats were subjected to CPB and randomly to receive vehicle (n = 8), ghrelin (n = 8), ghrelin plus [D-Lys3]-GHRP-6, a GHSR-1a inhibitor (n = 8), or ghrelin plus wortmannin, a phosphoinositide 3'-kinase (PI3K) inhibitor (n = 8). In vitro study was performed on cultured cardiomyocytes subjected to simulated cardiopulmonary bypass (SCPB). Ghrelin attenuated the inflammatory response, as evidenced by reduced induction of TNF-α, IL-6 and myocardial myeloperoxidase activity and concurrent reduction in apoptosis, oxidative stress, and levels of myocardial injury markers following CPB. Moreover, ghrelin significantly increased cardiac function after CPB. In cultured cardiomyocytes subjected to simulated CPB, ghrelin increased cell viability and decreased the percentage of apoptotic myocytes. Inhibition of ghrelin downstream signaling blocked the cardioprotective effects both in vivo and vitro. Ghrelin could provide an effective approach to the attenuation of CPB induced myocardial injury. The cardioprotective effects elicited by ghrelin may contribute to the inhibition of inflammatory response through the Akt-activated pathway.PLoS ONE 01/2013; 8(1):e55021. · 4.09 Impact Factor -
Article: Quadruple valve replacement with mechanical valves: an 11-year follow-up study.
[show abstract] [hide abstract]
ABSTRACT: We performed the first quadruple valve replacement with mechanical valves, combined with the correction of complex congenital heart disease on November 17, 1999. We report here the 11-year follow-up study. A 47-year-old man with subacute rheumatic endocarditis, a ventricular septal defect, and an obstruction of the right ventricular outflow tract required replacement of the aortic, mitral, tricuspid, and pulmonary valves; repair of the ventricular septal defect; and relief of the obstruction of the right ventricular outflow tract. The surgery was done on November 17, 1999, after careful systemic preparation of the patient. Warfarin therapy with a target international normalized ratio (INR) range of 1.5 to 2.0 was used. Follow-up included monitoring the INR, recording the incidences of thromboembolic and bleeding events, electrocardiography, radiography, and echocardiography evaluations. The patient's INR was maintained between 1.5 and 2.0. All 4 mechanical prosthetic heart valves worked well. He is in generally good health without any thromboembolic or bleeding complications. Long-term management is challenging for patients who have experienced quadruple valve replacement with mechanical valves; however, promising results could mean that replacement of all 4 heart valves in 1 operation is feasible in patients with quadruple valve disease, and an INR of 1.5 to 2.0 could be appropriate for Chinese patients with undergoing valve replacement with mechanical valves.Heart Surgery Forum 06/2012; 15(3):E145-9. · 0.63 Impact Factor -
Article: Induction of angiogenesis by controlled delivery of VEGF using nanoparticles.
[show abstract] [hide abstract]
ABSTRACT: AIMS: The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis. METHODS: The nanoparticles were prepared using phase separation method and the drug release profile was determined by ELISA study. The bioactivity of VEGF incorporated nanoparticles (VEGF-NP) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry. RESULTS: The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130±3.5 nm. The VEGF encapsulated was released in a bi-phase manner, with the majority of 69% released over 1-12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared to empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared to empty nanoparticles (both P<0.001), but it was much higher in VEGF-NP treated limbs (P<0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP treated limbs. CONCLUSIONS: Dex-GMA and gelatin based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis. ©2012 Blackwell Publishing Ltd.Cardiovascular Therapeutics 05/2012; · 2.35 Impact Factor -
Article: Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury.
[show abstract] [hide abstract]
ABSTRACT: Aims Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. Methods and results Reverse transcriptase-polymerized chain reaction and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. Conclusions This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy.European Heart Journal 05/2011; · 10.48 Impact Factor
