Biomedical subjects

Lilong Tang

Publications and source records attributed to Lilong Tang.

6 recordsLinked to original sources

PubMed2006

Granulation encapsulated stent: a new therapeutic approach for vascular implantation.

OBJECTIVES: To determine if stents could be encapsulated with immunocompatible granulation tissue for the treatment of vascular diseases. METHODS: Bare metal stents were implanted in New Zealand white rabbits so they would be encapsulated with immunocompatible granulation tissue. The granulation encapsulated stents (GES) were then treated with either mitomycin C or saline, and implanted into rabbit iliac arteries for 4 weeks. To test whether the effect of mitomycin C was retained, we co-cultured smooth muscle cells for 3 h with subcutaneous tissue (as control) or with granulation tissue from GES treated with mitomycin C and saline. RESULTS: Vessels with GES treated with mitomycin C (MS) and washed with saline had significantly less neointimal area (NA) after 4 weeks (0.27 (SD 0.03) mm(2) than vessels containing bare metal stents (B) (1.15 (SD 0.10) mm(2), n = 5, p<0.05) or GES treated with saline (S) (4.78 (SD 0.72) mm(2), n = 5, p<0.05). The average vessel injury score was not significantly different among these three groups (S: 1.98 (SD 0.51), MS: 1.46 (SD 0.18) and B: 1.51 (SD 0.32)). GES treated with saline had significantly less NA than the other two groups and also blocked blood flow in the contralateral iliac artery in the abdominal aortic bifurcation immediately after implantation and 4 weeks later. Histology also showed neointimal overgrowth in the vessel wall over the contralateral iliac artery. CONCLUSIONS: GES treated with mitomycin C can significantly inhibit neointimal formation in rabbit arteries due to the formation of granulation tissue. GES treated with saline demonstrated significantly increased NA and resisted normal rabbit artery pressures.

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PubMed2004

Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes.

The directed generation of cardiac myocytes from endogenous stem cells offers the potential for novel therapies for cardiovascular disease. To facilitate the development of such approaches, we sought to identify and exploit the pathways directing the generation of cardiac myocytes from adult rodent bone marrow cells (BMCs). In vitro cultures supporting the spontaneous generation of functional cardiac myocytes from murine BMCs demonstrated induced expression of platelet-derived growth factor (PDGF)-A and -B isoforms with alpha- and beta-myosin heavy chains as well as connexin43. Supplementation of PDGF-AB speeded the kinetics of myocyte development in culture by 2-fold. In a rat heart, myocardial infarction pretreatment model PDGF-AB also promoted the derivation of cardiac myocytes from BMCs, resulting in a significantly greater number of islands of cardiac myocyte bundles within the myocardial infarction scar compared with other treatment groups. However, gap junctions were detected only between the cardiac myocytes receiving BMCs alone, but not BMCs injected with PDGF-AB. Echocardiography and exercise testing revealed that the functional improvement of hearts treated with the combination of BMCs and PDGF-AB was no greater than with injections of BMCs or PDGF-AB alone. These studies demonstrated that PDGF-AB enhances the generation of BMC-derived cardiac myocytes in rodent hearts, but suggest that alterations in cellular patterning may limit the functional benefit from the combined injection of PDGF-AB and BMCs. Strategies based on the synergistic interactions of PDGF-AB and endogenous stem cells will need to maintain cellular patterning in order to promote the restoration of cardiac function after acute coronary occlusion.

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PubMed2003

Genetically engineered biologically based hemostatic bioassay.

Real-time direct measures of hemostatic parameters in vivo are required for optimizing the dynamic delivery of coagulation modifying pharmacotherapies. Typical sensors of physiologic functions in vivo, however, have only a restricted array of sensory inputs, and thus limited capacity to monitor thrombotic and hemostatic activity. To overcome this limitation we have developed a genetically engineered excitable cell line that can be potentially used for an implantable thrombin biosensor. Specifically, we have generated stem cell-derived cardiac myocyte aggregates overexpressing the human thrombin receptor, protease activated receptor-1 (PAR-1), which exploit the inherent electropotential input-output relationship of the cells to detect local changes in thrombin activity. In vitro, the signaling activity of PAR-1 cardiac myocytes was highly responsive to thrombin, inducing a sixfold increase in intracellular cAMP as compared with a twofold increase in control cells. In vivo, the engineered myocytes also detected alterations in local coagulation potential. Specifically, PAR-1 engineered cells implanted in vivo detected local increases in thrombin with a doubling in chronotropic activity compared with a 50% increase in control aggregates. Overall these studies demonstrate the potential of genetic engineering to expand the physiologic signals recognized by excitable cells, and may facilitate the translation of this approach for the real-time monitoring of hemostatic function in vivo.

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PubMed2002

Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function.

Delivery of young bone marrow-derived stem cells offers a novel approach for restoring the impaired senescent cardiac angiogenic function that may underlie the increased morbidity and mortality associated with ischemic heart disease in older individuals. Recently, we reported that alterations in endothelial cells of the aging heart lead to a dysregulation in the cardiac myocyte platelet-derived growth factor (PDGF)-B-induced paracrine pathway, which contributes to impaired cardiac angiogenic function. Based on these results, we hypothesized that cellular restoration of the PDGF pathway by bone marrow-derived endothelial precursor cells (EPCs) could reverse the aging-associated decline in angiogenic activity. In vitro studies revealed that young murine (3-month-old) bone marrow-derived EPCs recapitulated the cardiac myocyte-induced expression of PDGF-B, whereas EPCs from the bone marrow of aging mice (18-month-old) did not express PDGF-B when cultured in the presence of cardiac myocytes. Transplantation of young, but not old, genetically marked syngeneic bone marrow cells into intact, unirradiated aging mice that populated the endogenous senescent murine bone marrow incorporated into the neovasculature of subsequently transplanted syngeneic neonatal myocardium. Moreover, the young bone marrow-derived EPCs restored the senescent host angiogenic PDGF-B induction pathway and cardiac angiogenesis, with graft survival and myocardial activity in the aging murine host (cardiac allograft viability: 3-month-old controls, 8/8; 18-month-old controls, 1/8; 18-month-old donors receiving bone marrow from 3-month-old mice, 15/16; or 18-month-old mice, 0/6; P<0.05). These results may offer a foundation for the development of novel therapies for the prevention and treatment of cardiovascular disease associated with aging.

Aging↗

PubMed2002

Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model: feasibility of restoring impaired angiogenic capacity in the aging heart.

BACKGROUND: Compared with younger patients, myocardial infarction in the elderly has been associated with less favorable clinical outcomes, which may be attributable to a decline in angiogenic capacity in the aging heart. METHODS AND RESULTS: To test the hypothesis that the functional phenotype of cardiac microvascular endothelial cells is maintained partly by a cardiac myocyte platelet-derived growth factor (PDGF)-B-induced paracrine pathway, we conducted in vitro studies with murine cardiac cells. These studies demonstrated that unlike young endothelial cells, endothelial cells of the aging heart do not express PDGF-B when cultured in the presence of cardiac myocytes. The functional significance of this endothelial dysregulation was assessed with an ex vivo pinnal cardiac allograft model to demonstrate that senescent cardiac angiogenic activity was depressed (2 of 17 allografts were viable in 18-month-old mice versus 19 of 20 in 3-month-old mice; P<0.01). PDGF-AB pretreatment specifically restored the viability of the cardiac allografts in the aging hosts (13 of 13 allografts were viable; P<0.01 versus 18-month-old controls). Finally, in vivo studies in rat hearts demonstrated that pretreatment by intramyocardial delivery of PDGF-AB promotes angiogenesis and minimizes the extent of myocardial infarction in the aging hearts after coronary ligation (myocardial infarction size: 10.0 +/- 7.0% of left ventricular area in PDGF pretreatment [n=7] versus 17.6 +/- 5.6% in control [n=5] groups; P<0.03). CONCLUSION: Aging hearts have impaired angiogenic function as a result of depressed PDGF-B production. Restoration of the dysregulated endothelial PDGF-mediated angiogenic pathway in the aging heart reverses the senescent impairment in cardioprotective angiogenic function and offers a foundation for developing novel therapies for cardiovascular disease in older individuals.

Age Factors↗

PubMed2002

Enhanced myocyte-based biosensing of the blood-borne signals regulating chronotropy.

Biosensors play a critical role in the real-time determination of relevant functional physiological needs. However, typical in vivo biosensors only approximate endogenous function via the measurement of surrogate signals and, therefore, may often lack a high degree of dynamic fidelity with physiological requirements. To overcome this limitation, we have developed an excitable tissue-based implantable biosensor approach, which exploits the inherent electropotential input-output relationship of cardiac myocytes to measure the physiological regulatory inputs of chronotropic demand via the detection of blood-borne signals. In this study, we report the improvement of this application through the modulation of host-biosensor communication via the enhancement of vascularization of chronotropic complexes in mice. Moreover, in an effort to further improve translational applicability as well as molecular plasticity, we have advanced this approach by employing stem cell-derived cardiac myocyte aggregates in place of whole cardiac tissue. Overall, these studies demonstrate the potential of biologically based biosensors to predict endogenous physiological dynamics and may facilitate the translation of this approach for in vivo monitoring.

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