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Wangde Dai

Publications and source records attributed to Wangde Dai.

12 recordsLinked to original sources
PubMed2006

Myocardial regeneration by embryonic stem cell transplantation: present and future trends.

Embryonic stem cells are a promising source for myocardial regeneration due to their pluripotency and plasticity. In theory, embryonic stem cells are capable of self-renewal in an unlimited fashion, and can differentiate into any cell type required for cell-based therapy, including cardiac myocytes. In recent years, embryonic stem cells have been transplanted for cardiac regeneration in animal models, and the results are encouraging. However, there are still many hurdles to be overcome for the clinical application of embryonic stem cells.

Animals↗
PubMed2005

Stem cell transplantation for the treatment of myocardial infarction.

Stem cell transplantation provides a potential regenerative therapy for the heart damaged by myocardial infarction. Numerous scientific studies have been undertaken in animals and humans to analyze the safety and efficacy of this new approach. However, at the present time, the results have been mixed and inconclusive, and the mechanism of stem cell transplantation therapy remains unclear. This review discusses the controversies and problems that need to be addressed in future investigations.

Animals↗
PubMed2005

Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: a novel approach to preserve cardiac function after myocardial infarction.

OBJECTIVES: We determined whether collagen implantation could thicken the infarcted left ventricular (LV) wall and improve LV function. BACKGROUND: We hypothesized that thickening the infarcted wall by using collagen might result in some benefits that are similar to what previously had been reported when the infarcted wall was thickened with cells. METHODS: Fischer rats with one-week-old myocardial infarcts were injected with collagen or saline (100 microl) into the scar (n = 12 each group). Six weeks later, LV angiograms, hemodynamics, and regional myocardial blood flow were assessed. The hearts were processed for measurements of postmortem LV volume and histology. RESULTS: Collagen injection significantly increased scar thickness (719 +/- 26 microm) compared with the saline-treated group (440 +/- 34 microm, p = 2.6 x 10(-6)). By LV angiography, stroke volume was significantly larger in the collagen-treated group (163 +/- 8 microl) than in the saline-treated group (129 +/- 6 microl, p = 0.005), and LV ejection fraction was also greater in the collagen-treated group (48.4 +/- 1.8%) than in the saline-treated group (40.7 +/- 1.0%, p = 0.002). Analysis of regional wall motion demonstrated paradoxical systolic bulging in 5 of 10 saline-treated rats that averaged 20.3 +/- 2.6% of the LV diastolic circumference, but in none of the 11 collagen-treated rats (p = 0.012). The LV end-diastolic and end-systolic volumes were 319 +/- 12 microl and 190 +/- 7 microl in the saline-treated group, respectively. There was a trend for larger LV end-diastolic volumes (343 +/- 23 microl), but smaller end-systolic volumes (180 +/- 16 microl) in the collagen-treated group. CONCLUSIONS: This study shows that collagen injection thickens an infarct scar and improves LV stroke volume and ejection fraction, and prevents paradoxical systolic bulging after myocardial infarction.

Animals↗
PubMed2005

Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects.

BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to replace infarct scar, but the long-term effects are unknown. We studied short- and long-term effects of MSC transplantation on left ventricular (LV) function in a rat myocardial infarction model. METHODS AND RESULTS: Saline (n=46) or MSCs labeled with 1,1'-dioctadecyl-3,3,3'3'-testramethylindocarbocyanine perchlorate (DiI; n=49, 2x10(6) cells each) were injected into the scar of a 1-week-old myocardial infarction in Fischer rats. The presence and differentiation of engrafted cells and their effect on LV ejection fraction was assessed. At 4 weeks, LV stroke volume was significantly greater in the MSC-treated group (145+/-9 microL) than in the saline group (122+/-3 microL, P=0.032), and LV ejection fraction was significantly greater in MSC-treated animals (43.8+/-1.0%) than in the saline group (38.8+/-1.1%, P=0.0027). However, at 6 months, these benefits of MSC treatment were lost. DiI-positive cells were observed in the MSC group at 2 weeks and at 3 and 6 months. Expression of the muscle-specific markers alpha-actinin, myosin heavy chain, phospholamban, and tropomyosin was not observed at 2 weeks in DiI-positive cells. At 3 and 6 months, the DiI-positive cells were observed to express the above muscle-specific markers, but they did not fully evolve into an adult cardiac phenotype. Some of the DiI-positive cells expressed von Willebrand factor. CONCLUSIONS: Allogeneic MSCs survive in infarcted myocardium as long as 6 months and express markers that suggest muscle and endothelium phenotypes. MSCs improved global LV function at 4 weeks; however, this benefit was transient, which suggests a possible early paracrine effect.

Animals↗
PubMed2005

Neointimal hyperplasia on a cell-seeded polytetrafluoroethylene graft is promoted by transfer of tissue plasminogen activator gene and inhibited by transfer of nitric oxide synthase gene.

OBJECTIVE: The objective of this study was to examine the effect of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase (eNOS) on thrombosis and neointimal hyperplasia on a polytetrafluoroethylene (PTFE) graft seeded with smooth muscle cells (SMCs). METHODS: SMCs retrovirally transduced with tPA and eNOS genes were seeded on PTFE grafts and then implanted into the infrarenal rabbit aorta. Thrombosis and neointimal hyperplasia on the grafts were examined after 30 and 100 days of implantation. RESULTS: At 30 days of implantation, thrombus was observed on the luminal surface of both unseeded and SMC seeded control grafts, whereas grafts seeded with SMCs secreting tPA were nearly free of thrombus. At 100 days, the neointima on grafts seeded with tPA transduced SMCs was significantly thicker (925 +/- 150 microm, n = 5) than neointima on the other grafts (range, 132 to 374 microm; P < .001). Neointima thickness on grafts seeded with eNOS transduced SMCs (154 +/- 27 microm) was similar to that of unseeded grafts (132 +/- 16 microm, P > .05); both were thinner than those on grafts seeded with SMCs transduced with only lacZ gene (287 +/- 35 microm). The ratio of seeded cells in the neointima was significantly higher on SMC/tPA grafts (46% +/- 8%) than SMC/NOS grafts (21% +/- 6%, P < .05), indicating tPA transduced cells proliferated more than eNOS transduced cells. CONCLUSIONS: Engineered tPA expression in seeded SMCs causes significantly more neointimal hyperplasia, despite the favorable inhibition of luminal thrombus. eNOS expression in the seeded cells inhibits neointimal hyperplasia.

Animals↗
PubMed2004

Implantation of immature neonatal cardiac cells into the wall of the aorta in rats: a novel model for studying morphological and functional development of heart cells in an extracardiac environment.

BACKGROUND: Morphological and functional development of implanted neonatal cardiac cells in the wall of the abdominal aorta in rats was investigated. METHODS AND RESULTS: Cardiomyocytes from neonatal Fischer rats (both sexes) or medium were injected into the wall of the abdominal aorta in female Fischer rats (n=22 in each group). Two or 6 weeks later, the grafted site was exposed and fixed for histological and immunohistological examination. Polymerase chain reaction analysis of the SRY gene to identify male cells was performed in the treated aortas. Seven of 10 cell-treated aortas but none of 10 medium-treated aortas showed spontaneous rhythmic beating at the grafted site after excision of the heart at 2 weeks. Polymerase chain reaction of the SRY gene was positive in 3 cell-treated aortas and none of 3 medium-treated aortas at 6 weeks. Hematoxylin-and-eosin staining showed viable grafts in 9 of 10 aortas at 2 weeks and 9 of 9 aortas at 6 weeks in the cell-treated group but in none of the aortas receiving medium. Neonatal cardiomyocytes in the graft formed compact, longitudinally oriented cardiac muscle bundles and had cross-striations and vascularization. Immunohistochemical staining for sarcomeric actin was positive in 4 of 10 aortas at 2 weeks and 9 of 9 aortas at 6 weeks in the cell group but in none of the aortas in the medium group. CONCLUSIONS: Grafted neonatal cardiomyocytes survive, differentiate, grow, develop a blood supply, and spontaneously contract within the wall of the aorta in rats.

Animals↗
PubMed2004

Relationship between cyclooxygenase-2 inhibition and thrombogenesis.

Recently there has been considerable interest in the role of cyclooxygenase-2 (COX-2) in thrombosis and myocardial infarction. A large number of clinical and basic studies have focused on whether COX-2 inhibitors can induce a prothrombotic disorder and increase the risk of cardiovascular thrombosis. This article reviews (1) the roles of COX-2 in the metabolism of prostaglandins; (2) the influence of COX-2 inhibition in the platelet aggregation and the antithrombotic function of vascular endothelium; (3) the roles of COX-2 inhibition in atherothrombosis; and (4) clinical trials that examine COX-2 inhibition in relationship to the risk of myocardial infarction. Based on the published data, this review suggests that COX-2 plays varying and sometimes conflicting roles in thrombogenesis, in prostaglandins' metabolism of endothelium in healthy or dysfunctional conditions, and in atherothrombosis. Future investigations under different pathologic conditions are needed to fully understand the net effect of COX-2 inhibition on thrombogenesis. The roles of COX-2 in the pathophysiologic process of cardiovascular thrombosis are diverse and controversial, and need to be further studied to guide clinical practice.

Cyclooxygenase 2↗
PubMed2003

Transplantation of neonatal cardiomyocytes after permanent coronary artery occlusion increases regional blood flow of infarcted myocardium.

BACKGROUND: Cellular cardiomyoplasty is a promising approach for rebuilding scar tissue after acute myocardial infarction. However, the angiogenic potential of transplanted immature cardiomyocytes and their effect on regional myocardial blood flow (RMBF) after coronary artery occlusion remain to be evaluated. METHODS AND RESULTS: Intramyocardial injection of cultured neonatal cardiomyocytes (4 x 10(6) cells/50-70 microliter) into the scar 1 week after permanent coronary occlusion in rats resulted in improved RMBF in the infarct 4 weeks after transplantation (radioactive microspheres, 0.97 +/- 0.18 ml/min/g) in comparison to medium-injected hearts (0.61 +/- 0.11 ml/min/g, P < 0.047). The macroscopic perfusion defect after in vivo staining with the blue dye 50% Uniperse blue was significantly smaller in the cell transplantation group (1.5 +/- 0.3% of the heart) compared to the medium group (3.0 +/- 0.6%, P < 0.017). Clusters of engrafted cells within the scar demonstrated a high capillary density (1217 +/- 114 perfused (blue) capillaries/mm(2)); however, in the scar tissue itself capillary density in the cell group (156 +/- 62/mm(2)) did not significantly differ from the medium group (125 +/- 10/mm(2)), suggesting that neo-angiogenesis was confined to regions of successful engraftment (non-infarcted tissue: 1924 +/- 114 perfused capillaries/mm(2)). The transplantation group was characterized by smaller diastolic and systolic left ventricular volumes, as assessed by intravenous ventriculography, along with thickened infarcts (0.93 +/- 0.07 vs. 0.75 +/- 0.04 mm, P < 0.020) and lower infarct expansion indices (0.64 +/- 0.07 vs. 0.83 +/- 0.06, P < 0.023), as determined by post-mortem morphometry of histologic slides. CONCLUSIONS: Transplantation of neonatal cardiomyocytes induced neo-angiogenesis in zones of successful cell engraftment within the scar, which effectively enhanced tissue perfusion.

Animals↗
PubMed2003

Smooth muscle cells improve endothelial cell retention on polytetrafluoroethylene grafts in vivo.

OBJECTIVE: We investigated the influence of smooth muscle cells (SMC) on endothelial cell (EC) retention on polytetrafluoroethylene (PTFE) grafts and the effect of SMC seeding on intimal hyperplasia in vivo in a rabbit model. METHODS: Fibronectin-coated PTFE grafts (4 mm diameter) were seeded with either EC alone, SMC alone, or SMC followed 24 hours later by EC. The grafts were connected to an extracorporal aortic shunt for 1 hour or were individually implanted for 1, 30, and 100 days into the infrarenal aorta as an end-to-side bypass graft. The number of retained cells was compared at 1 hour and at 1 day after implantation. Neointimal thickness was measured 30 and 100 days after implantation. RESULTS: After 1-hour exposure to blood flow, EC retention rate was greater (P <.005) if seeded on top of SMC (98% +/- 2%; n = 8) versus being seeded alone (65 +/- 11%; n = 8). SMC retention rate was 95 +/- 5% (n = 8) when seeded alone. Similar cell retention was obtained 1 day after implantation. After 30-day implantation the neointima was thicker in grafts seeded with EC and SMC (282 +/- 136 microm; n = 3) than with EC only (52 +/- 45 microm; n = 3; P <.001). However, the neointimal thickness for dual-cell-seeded grafts (126 +/- 60 microm; n = 3) was not significantly different (P =.09) from EC-seeded grafts (79 +/- 48 microm; n = 3) after 100-day implantation. CONCLUSION: EC retention on PTFE grafts in vivo is improved if seeded over a layer of SMC. Further studies are needed to determine whether overlying EC modulate proliferation of underlying SMC.

Animals↗
PubMed2003

Effects of acetaminophen on myocardial infarct size in rats.

OBJECTIVE: Acetaminophen is widely prescribed as an analgesic agent in hospitals and clinics. However, acetaminophen theoretically could influence myocardial infarct size by reducing prostaglandin synthesis in vivo. To date, the effect of acetaminophen on myocardial infarct size is unknown. The present study investigated (1) whether acetaminophen has any effect on myocardial infarct size when given in an analgesic dose and (2) whether acetaminophen can affect the cardioprotective effect of the early phase of ischemic preconditioning in rats. METHODS: Female Sprague-Dawley rats were randomly assigned to four groups (n=12 each). Group 1 (no preconditioning): Vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to ischemia. Group 2 (acetaminophen plus no preconditioning): intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to ischemia. Group 3 (preconditioning): The heart was preconditioned before ischemia, and the vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to the ischemia. Group 4 (acetaminophen plus preconditioning): The heart was preconditioned before ischemia, and intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to the ischemia. The preconditioning protocol consisted of three cycles of 3 minutes of coronary occlusion and 5 minutes of reperfusion. The left coronary artery was then occluded for 60 minutes, followed by 3 hours of reperfusion. The end points were hemodynamics, body temperature, and risk area and area of necrosis of the left ventricle. RESULTS: The area of risk was similar among the four groups. The area of necrosis, expressed as a percentage of the area at risk, was 55.7% +/- 6.1% in the no-preconditioning group, 62.8% +/- 2.4% in the acetaminophen plus no-preconditioning group, 24.7% +/- 7.3% in the preconditioning group, and 17.2% +/- 6.4% in the acetaminophen plus preconditioning group. The area of necrosis/area at risk was decreased significantly in the preconditioning group and in the acetaminophen plus preconditioning group compared with the no-preconditioning group (P<.05); but there were no significant differences between the no-preconditioning group and the acetaminophen plus no-preconditioning group (P=.29), or between the preconditioning group and acetaminophen plus preconditioning group (P=.45). Among the four groups, heart rate and body temperature were similar. The infusion of the vehicle or acetaminophen increased blood pressure in the four groups, but to a lesser extent in the acetaminophen group. However, during coronary artery occlusion and reperfusion, the four groups had comparable blood pressures. CONCLUSION: Acetaminophen had no beneficial or adverse effects on infarct size in nonpreconditioned rats, and the beneficial effects of preconditioning were not blocked or prevented by acetaminophen at this analgesic dose.

Acetaminophen↗
PubMedDate not supplied

Stem cell therapy for the heart.

Cellular cardiomyoplasty is an expanding field of research that involves numerous types of immature cells administered via several modes of delivery. The purpose of this review is to investigate the benefits of different types of cells used in stem cell research as well as the most efficient mode of delivery. The authors also present data showing that stem cells isolated from bone marrow are present at both 2 weeks and 3 months after engraftment in a myocardial infarction. These cells express muscle markers at both time points, which suggests that they have begun to differentiate into cardiomyocytes. Several questions must be answered, however, before stem cells can be used routinely in the clinic. Once these questions have been addressed, the use of stem cells in clinical practice can be realized.

Animals↗