PubMed Health⌕ Search

Biomedical subjects

Tao-Sheng Li

Publications and source records attributed to Tao-Sheng Li.

32 records · Page 2Linked to original sources
PubMed2003

Low angiogenic potency induced by the implantation of ex vivo expanded CD117(+) stem cells.

Ex vivo expansion of stem cells might be a feasible method of resolving the problem of limited cell supply in cell-based therapy. The implantation of expanded CD34(+) endothelial progenitor cells has the capacity to induce angiogenesis. In this study, we tried to induce angiogenesis by implanting expanded CD117(+) stem cells derived from mouse bone marrow. After 2 wk of culture with the addition of several growth factors, the CD117(+) stem cells expanded approximately 20-fold and had an endothelial phenotype with high expression of CD34 and vascular endothelial-cadherin. However, >70% of these ex vivo expanded cells had a senescent phenotype by beta-galactosidase staining, and their survival and incorporation were poor after implantation into the ischemic limbs of mice. Compared with the PBS injection only, the microvessel density and the percentage of limb blood flow were significantly higher after the implantation of 2 x 10(5) freshly collected CD117(+) cells (P < 0.01) but not after the implantation of 2 x 10(5) expanded CD117(+) cells (P > 0.05). These data indicate that ex vivo expansion of CD117(+) stem cells has low potency for inducing therapeutic angiogenesis, which might be related to the cellular senescence during ex vivo expansion.

Aging↗
PubMed2003

Long-term survival of xenografted neonatal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression and CD40 blockade.

BACKGROUND: Prolonged survival of xenografted neonatal cardiomyocytes was achieved by blocking the CD28/B7 costimulatory pathway via CTLA4-Ig gene transfer. We examined the long-term survival of xenografted neonatal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression and transient CD40 blockade with anti-CD40L monoclonal antibody (MR1). METHODS AND RESULTS: Neonatal cardiomyocytes derived from Dark Agouti rats were infected with CTLA4-Ig-expressing adenovirus vectors and injected directly into the normal myocardium of C3H/He mice. Mice were also given an intraperitoneal injection of 500 microg MR1 (CTLA+MR group, n=30) or control immunoglobulin (CTLA group, n=30) 1 hour before and 1, 3, and 7 days after cardiomyocyte implantation. As a control, cells infected with beta-Gal-expressing adenovirus vector (RL group, n=15) and cells without infection (control group, n=15) were injected into additional mice. Mice from all groups were killed 2, 4, and 8 weeks after xenotransplantation, and mice from the CTLA+MR and CTLA groups were killed 4 and 6 months after xenotransplantation. Neonatal cardiomyocytes were successfully infected by adenovirus vectors. Immunohistochemical analysis showed that the xenografted cardiomyocytes survived and expressed CTLA4-Ig for 6 months in all mice from the CTLA+MR and CTLA groups. A gap junction between the xenografted and host cardiomyocytes was also confirmed. Conversely, neonatal cardiomyocytes did not survive for even 2 weeks after xenotransplantation in the mice from the RL and control groups. CONCLUSIONS: Long-term survival of xenografted neonatal cardiomyocytes was achieved by adenovirus-mediated CTLA4-Ig expression and transient CD40 blockade.

Abatacept↗
PubMed2003

Independent predictive value of the overall number of metastatic N1 and N2 stations in lung cancer.

OBJECTIVE: The number of metastatic N2 stations is a known prognostic factor in patients with non-small-cell lung cancer (NSCLC). However, involvement of N1 stations as well as that of N2 stations seems to be important in the prognosis of these patients. We therefore attempt to clarify the significance of the total number of metastatic stations in pathologic N1 and N2 NSCLCs. METHODS: Patients with either pathologic N1 (n = 51) or N2 (n = 96) NSCLC who had undergone major pulmonary resection with complete mediastinal dissection were included in this retrospective study. All positive nodes were characterized by location according to the TNM classification system. The hilar station was included with the N2 stations. RESULTS: The total number of metastatic stations in patients with N2 disease ranged from 1 to 8 (average 2.5), whereas that in patients with N1 disease ranged from 1 to 3 (average 1.2). The incidence of multiple-station metastasis (> or = 3 metastatic stations) among N2 patients (35%) was significantly higher than that among N1 patients (2%) (p < 0.001). Multivariate analysis of survival showed pathologic N1 status (relative risk = 0.443, p = 0.013) and < or = 2 metastatic stations (relative risk = 0.515, p = 0.020) to be significant and independent prognostic factors. Age, sex, cell type, resected lobe, and pathological T status were statistically insignificant determinates of survival. CONCLUSIONS: The total number of metastatic stations (< or = 2 vs > or = 3) is an independent prognostic indicator in patients with completely resected pathologic N1 or N2 NSCLC. The number of metastatic stations will be useful as a stratification factor in prospective clinical trials of these patients.

Aged↗
PubMed2003

Enhanced tumor necrosis factor- alpha expression in small sized abdominal aortic aneurysms.

Circulating levels of tumor necrosis factor alpha (TNF- alpha) are elevated in the patients with abdominal aortic aneurysm (AAA). We investigated TNF- alpha expression and cellular infiltration in the walls of AAAs of different sizes. Twenty-seven surgical specimens of AAAs were categorized according to the maximum aneurysm diameter into a small size group (less than 50 mm in diameter, n = 8; S group), a medium-sized group (50 to 59 mm in diameter, n = 11; M group), and a large size group (larger than 59 mm in diameter, n = 8; L group). The level of TNF- alpha and interleukin-1 beta(IL-1 beta) in the aneurysm wall was measured by ELISA. Immunohistochemical staining was performed to observe the TNF- alpha expression and the infiltration of macrophages and lymphocytes in aneurysm walls. Enzyme-linked immunosorbent assay showed that the level of TNF- alpha in the S group (5.47 +/- 3.48 pg/mg protein) was significantly higher ( p < 0.05) than that in the M group (2.70 +/- 1.33 pg/mg protein) or the L group (1.82 +/- 1.21 pg/mg protein). No significant difference in IL-1 beta was observed between the S, M, and L groups. Immunohistochemical analysis also showed that TNF- alpha was expressed strongly in the S group but was negative or weakly positive in the M and L groups. Furthermore, the expression of TNF- alpha was seen mainly where the aneurysm wall showed atheromatous change and macrophage infiltration. These results indicated that the expression of TNF- alpha in the aneurysm wall was enhanced in small AAAs, and this enhancement might be related to the infiltration of macrophages.

Aorta, Abdominal↗
PubMed2003

Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model.

BACKGROUND: Local bone marrow cell implantation can induce angiogenesis. In the present study we investigated whether angiogenesis induced by bone marrow cell implantation improves deteriorated cardiac function in a rat heart model of hypoperfusion. METHODS: A hypoperfusion heart model was created in Dark Agouti rats by ligating the left anterior descending artery placed against a copper wire (phi275 microm), then pulling out the wire immediately. The left ventricular (LV) anterior wall was injected directly at six points, each with 1 x 10(7) bone marrow cells in 10 microL of phosphate-buffered saline or with phosphate-buffered saline only, respectively. Echocardiography was performed to evaluate the cardiac function 7, 30, 60, and 90 days after treatment. Microvessel density and blood flow in the LV anterior wall were estimated 60 days after treatment. RESULTS: Both the increase of LV end-systolic diameter and the decrease of percent of fractional shortening caused by myocardial ischemia were attenuated effectively by bone marrow cell implantation treatment. Bone marrow cell implantation treatment also increased the levels of angiopoietin-1 and vascular endothelial growth factor in the LV anterior wall. The microvessel density, blood flow, and thickness of the LV anterior wall significantly also increased after bone marrow cell implantation treatment compared with those after phosphate-buffered saline injection. CONCLUSIONS: The local implantation of autologous bone marrow cells induced angiogenesis and improved the perfusion of ischemic myocardium, thereby preventing LV remodeling and improving deteriorated cardiac function caused by myocardial hypoperfusion.

Angiogenesis Inducing Agents↗
PubMed2003

CD117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation.

Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells. We investigated the roles of mature mononuclear cell and stem cell fractions in bone marrow in this treatment. Although CD34 is the most popular marker for stem cell selection for inducing therapeutic angiogenesis, we separated CD117-positive cells (CD117+) from mature bone marrow mononuclear cells [CD117-negative cells (CD117-)] from mice using the antibody to the stem cell receptor, because some of the bone marrow stem cells that express CD117+ and CD34- might generate angiogenic cytokines and differentiate into endothelial cells. The angiogenic potency of CD117+ and CD117- cells was investigated in vitro and in vivo. Significantly higher levels of VEGF were secreted from the CD117+ cells than from the CD117- cells (P < 0.001). Most of the CD117- cells died, but the CD117+ cells grew well and differentiated into endothelial cells within 14 days of culture. The CD117+ cells survived and were incorporated in microvessels within 14 days of being implanted into the ischemic hindlimbs of mice, but the CD117- cells did not. The microvessel density and blood perfusion of the ischemic hindlimbs were significantly higher in the CD117+ cell-implanted mice than in the CD117- cell-implanted mice (P < 0.01). The microvessel density in ischemic hindlimbs was also significantly higher in the CD117+ cell-implanted mice than in the total bone marrow cell-implanted mice (P < 0.05). Thus CD117+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.

Animals↗
PubMed2002

Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model.

The angiogenic effect induced by autologous bone marrow cell implantation (BMCI) was examined in the ischemic hindlimbs of diabetic and nondiabetic rats. Diabetes mellitus was induced by the systemic administration of streptozotocin. We investigated the production of angiogenic factors and endothelial differentiation from bone marrow cells and the native recovery of blood flow in the ischemic hindlimbs. To observe the angiogenic effect induced by BMCI treatment, 6 x 10(7) bone marrow cells were injected intramuscularly at six points into the ischemic limbs, and regional perfusion recovery was evaluated with colored microspheres 2 wk later. No difference was found between diabetic and nondiabetic rats in the release of angiogenic factors or endothelial differentiation from bone marrow cells in vitro. The levels of nitric oxide in plasma were significantly lower, and native perfusion recovery in the ischemic hindlimbs was significantly slower in the diabetic rats than in the nondiabetic rats. However, although perfusion recovery was achieved in the ischemic hindlimbs, there was no significant increase in systemic VEGF after BMCI treatment in either the diabetic or nondiabetic rats. Therefore, therapeutic angiogenesis induced by BMCI could be a safe and effective treatment for ischemic limb disease in diabetic patients.

Animals↗
PubMed2002

Angiogenesis induced by the injection of peripheral leukocytes and platelets.

BACKGROUND: Peripheral leukocytes and platelets (LAPs) contain many kinds of cells with the ability to secrete several growth factors and cytokines. We attempted to induce therapeutic angiogenesis by injecting self-LAPs into a rat ischemic hindlimb model. MATERIALS AND METHODS: Supernatants from cultured LAPs were used for the endothelial cell (EC) proliferation assay, and LAPs were used in a cornea model to evaluate angiogenic potency. LAPs were injected directly into the male Dark Agouti rat ischemic hindlimb model, after which a microangiogram was done and the capillary/muscle fiber ratio was examined histologically. ELISA revealed the levels of contributing growth factors and cytokines present in the ischemic muscles. RESULTS: The EC proliferation assay showed that the supernatants of LAPs accelerated proliferation and that the LAPs induced angiogenesis in the cornea model. The microangiograms and histological evaluation revealed that angiogenesis was induced more effectively in the rats injected with LAPs (LAP group) than in the those injected with phosphate-buffered saline (PBS group). The levels of basic fibroblast growth factor (bFGF) in the ischemia, PBS, and LAP groups were significantly increased compared to those in the sham group. The level of interleukin-1beta (IL-1beta) in the LAP group was significantly more elevated than in the other groups. CONCLUSIONS: The injection of self-LAPs induced angiogenesis in a rat ischemic hindlimb model. Ischemia caused an elevation in the level of bFGF and also in IL-1beta derived from LAPs, which contributed to angiogenesis. This is a novel, yet simple and safe method of inducing therapeutic angiogenesis.

Animals↗
PubMed2002

Can nonpenetrating vascular closure staples and hepatocyte growth factor prevent intimal hyperplasia following ePTFE grafting of the carotid artery in rabbits?

PURPOSE: To evaluate whether nonpenetrating vascular closure staples (VCS) and hepatocyte growth factor (HGF) can effectively prevent anastomotic intimal hyperplasia. METHODS: An expanded polytetrafluoroethylene graft, 2 mm in diameter, was implanted in the common carotid artery of rabbits divided into three experimental groups. In the control group, distal anastomosis was performed with interrupted suturing; in the VCS group, clips were applied along the lateral suture line after the placement of stay sutures; and in the VCS + HGF group, the same anastomotic technique was performed as in the VCS group, followed by the administration of the HGF for 4 days. RESULTS: The time taken to complete the anastomosis was significantly less in both the VCS groups than in the control group ( P < 0.0001). On postoperative day (POD) 28, the patency rate was significantly lower ( P < 0.05) in the VCS group (42.9%) than in the control group (100%), but the rate in the VCS + HGF group (100%) was the same as that in the control group. Intimal thickness was significantly less in the control group than in either the VCS or VCS + HGF groups ( P< 0.05). The percentage of area stenosis was significantly less ( P< 0.01) in the control group than in the VCS group. CONCLUSION: The VCS clip failed to suppress intimal thickness or reduce the percentage of stenosis at the anastomotic site.

Anastomosis, Surgical↗
PubMed2002

Therapeutic angiogenesis induced by local autologous bone marrow cell implantation.

BACKGROUND: Therapeutic angiogenesis was induced by local autologous bone marrow cell implantation (BMCI) in ischemic hindlimb or ischemic heart models in rats. This study was designed to investigate the toxicity and therapeutic potency of local BMCI using a chronic coronary occlusion model in dogs. METHODS: The canine chronic coronary occlusion model was created by ligating of the left anterior descending artery (LAD). The myocardium in the left ventricle was divided into distinct normal, marginal, and infarction areas 30 days after LAD ligation. Each area was injected at two locations, with either 2 x 10(7) bone marrow cells (n = 7, BMCI group) or 0.1 mL phosphate-buffered saline (PBS) only (n = 7, PBS group), respectively. Hemodynamics were evaluated by a single ultrasonic transducer and echocardiography before and 30 days after the treatment. Angiogenesis was evaluated by vessel count 30 days after the treatment. The toxicity of BMCI treatment was also evaluated in 8 normal dogs by following changes in electrocardiography (ECG), echocardiography, local histology, and systemic biochemistry indexes. RESULTS: There was a significantly higher percentage of wall thickening in the marginal area in the BMCI group than in the PBS group 30 days after treatment (14.5 +/- 2.28 versus 8.1 +/- 3.00, p = 0.002). Significantly more microvessels were observed in the marginal area in the BMCI group than in the PBS group 30 days after treatment (127.7 +/- 20.1 versus 88.0 +/- 10.2/field, p = 0.0007). No systemic or local toxicity was found following BMCI treatment in the acute or chronic phases. CONCLUSIONS: BMCI treatment improved local wall thickening dynamics, presumably due to the angiogenesis induced by the treatment. This indicates that it might be a safe and effective therapy for ischemic heart disease.

Animals↗
PubMed2002

Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats.

Therapeutic angiogenesis can be induced by local implantation of bone marrow cells. We tried to enhance the angiogenic potential of this treatment by ex vivo hypoxia stimulation of bone marrow cells before implantation. Bone marrow cells were collected and cultured at 33 degrees C under 2% O(2)-5% CO(2)-90% N(2) (hypoxia) or 95% air-5% CO(2) (normoxia). Cells were also injected into the ischemic hindlimb of rats after 24 h of culture. Hypoxia culture increased the mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, and fetal liver kinase-1 (Flk-1) from 2.5- to fivefold in bone marrow cells. The levels of VEGF protein in the ischemic hindlimb were significantly higher 1 and 3 days after implantation with hypoxia-cultured cells than with normoxia-cultured or noncultured cells. The microvessel density and blood flow rate in the ischemic hindlimbs were also significantly (P < 0.001) higher 2 wk after implantation with hypoxia-cultured cells (89.7 +/- 5.5%) than with normoxia-cultured cells (67.0 +/- 9.6%) or noncultured cells (70.4 +/- 7.7%). Ex vivo hypoxia stimulation increased the VEGF mRNA expression and endothelial differentiation of bone marrow cells, which together contributed to improved therapeutic angiogenesis in the ischemic hindlimb after implantation.

Animals↗
PubMed2002

Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease.

Neovascularization has recently been used as a new treatment for severe ischemic disease. We tried to induce therapeutic neovascularization by autologous bone marrow cell implantation (BMCI) in eight selected patients with chronic peripheral arterial disease (PAD), in whom traditional treatments had failed. Improvement of subjective symptoms was seen in seven patients after treatment. Of three limbs with toe or finger ulceration, complete healing was achieved in two, while the other one became less severe after treatment. No relative toxicity was observed in any of the patients. BMCI might be a feasible treatment for selected patients with chronic PAD.

Aged↗
PubMedDate not supplied

The safety and feasibility of the local implantation of autologous bone marrow cells for ischemic heart disease.

BACKGROUND AND AIMS: Local autologous bone marrow cell implantation (BMCI) can induce therapeutic angiogenesis. We evaluated the safety and feasibility of this treatment for ischemic heart disease. METHODS: The safety of BMCI was preclinically confirmed in dogs by giving a direct injection of either 2 x 10(7) bone marrow cells (n = 4) suspended in 0.1 mL phosphate-buffered saline (PBS), or 0.1 ml PBS only (n = 4, PBS group), into the myocardium of the left ventricle at six points. Electrocardiograph (ECG), echocardiography, and systemic biochemistry indexes were recorded 1, 7, 30, and 240 days after treatment, and histological change was examined 240 days after treatment. We also evaluated the clinical safety and feasibility of BMCI in six patients with ischemic heart disease, who were given BMCI treatment in combination with coronary artery bypass grafting (CABG), by recording Holter ECG, echocardiography, computed tomography, and systemic biochemistry indexes in the acute and chronic phases after treatment. RESULTS: No significant changes in systemic biochemistry indexes were found after BMCI treatment in comparison with control groups, in either the experimental investigation or the clinical trial. No cardiac damage related to BMCI was detected by ECG or echocardiography, and histological examination showed minimal fibrotic change within the myocardium after BMCI or PBS injection in the dogs. Local calcification was not detected on histological slices 240 days after treatment in the dogs, or on computed tomography 1 year after treatment in the patients. CONCLUSIONS: BMCI treatment appears to be a safe and feasible method of inducing angiogenesis to treat ischemic heart disease

Animals↗