Biomedical subjects

Yongzhong Wang

Publications and source records attributed to Yongzhong Wang.

17 recordsLinked to original sources

PubMed2007

[Therapy with stem cells for acute ischemic heart disease: myocardial regeneration?].

Treatment of ischemic heart disease with injections of bone-marrow-derived stem cells is a promising new modality. However, recent medium-sized placebo controlled trials in patients with acute myocardial infarction have not been conclusive regarding the treatment effect. This short review aims to elucidate some of the unresolved issues raised by the first clinical trials. These include long-term safety, tissue-distribution of infused cells, selecting the optimal cell type and number, timing of the treatment, and the mechanism of a potential treatment effect.

Clinical Trials as Topic↗

PubMed2006

Circulating angiogenic cytokines and stem cells in patients with severe chronic ischemic heart disease--indicators of myocardial ischemic burden?

BACKGROUND: Angiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease. METHODS: Fifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects. RESULTS: Plasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34-/CD45- cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p<0.005-0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p=0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea. CONCLUSIONS: Plasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.

Adult↗

PubMed2006

Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy?

Mobilization of stem cells into the peripheral circulation for myocardial regeneration using subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) has been tested in both patients with acute myocardial infarction (AMI) and patients with chronic myocardial ischaemia. G-CSF treatment seems to be safe and unblinded trials in patients with AMI were encouraging. However, larger double-blind placebo-controlled trials have not been able to demonstrate effect of G-CSF treatment. In patients with chronic myocardial ischaemia, small-unblinded G-CSF trials did not show effect on myocardial perfusion and function. In both patient populations, G-CSF did mobilize stem cells of known importance to myocardial regeneration, but there seemed to be a general lack of homing of the stem cells into the ischaemic myocardium. In AMI, factors of importance to homing of stem cells, stem cell derived factor-1, are maximally elevated in plasma 3 weeks after infarction, suggesting that this time point could be the optimal time for stem cell mobilization treatment. The known complex interaction of stem cells and cytokines for induction of vasculogenesis should be implemented in future clinical trials, to elucidate whether G-CSF mobilization of stem cells might be useful as a new regenerative treatment in patients with ischaemic heart disease.

Acute Disease↗

PubMed2006

Stem cell-based tissue engineering with silk biomaterials.

Silks are naturally occurring polymers that have been used clinically as sutures for centuries. When naturally extruded from insects or worms, silk is composed of a filament core protein, termed fibroin, and a glue-like coating consisting of sericin proteins. In recent years, silk fibroin has been increasingly studied for new biomedical applications due to the biocompatibility, slow degradability and remarkable mechanical properties of the material. In addition, the ability to now control molecular structure and morphology through versatile processability and surface modification options have expanded the utility for this protein in a range of biomaterial and tissue-engineering applications. Silk fibroin in various formats (films, fibers, nets, meshes, membranes, yarns, and sponges) has been shown to support stem cell adhesion, proliferation, and differentiation in vitro and promote tissue repair in vivo. In particular, stem cell-based tissue engineering using 3D silk fibroin scaffolds has expanded the use of silk-based biomaterials as promising scaffolds for engineering a range of skeletal tissues like bone, ligament, and cartilage, as well as connective tissues like skin. To date fibroin from Bombyx mori silkworm has been the dominant source for silk-based biomaterials studied. However, silk fibroins from spiders and those formed via genetic engineering or the modification of native silk fibroin sequence chemistries are beginning to provide new options to further expand the utility of silk fibroin-based materials for medical applications.

Animals↗

PubMed2006

Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease.

AIMS: To assess the safety and effects of combined treatment with vascular endothelial growth factor-A(165) plasmid (VEGF-A(165)) and granulocyte- colony stimulating factor (G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD). METHODS AND RESULTS: Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A(165) plasmid followed 1 week later by G-CSF (10 microg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A(165) plasmid and (ii) sixteen patients treated with intramyocardial injections of placebo. In the G-CSF group, circulating CD34+ stem cells increased almost 10-fold compared with the control groups (P<0.0001). After 3 months, there was no improvement in myocardial perfusion at single photon emission computerized tomography in the VEGF-A(165) and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy. CONCLUSION: Intramyocardial VEGF-A(165) gene transfer followed by bone marrow stem cell mobilization with G-CSF seemed safe. However, a significant increase in circulating stem cells did not lead to improved myocardial perfusion or clinical effects suggesting a neutral effect of the treatment. To improve homing of stem cells, higher doses of VEGF-A(165) and/or use of SDF-1 transfer might be considered.

Adolescent↗

PubMed2006

Cartilage tissue engineering with silk scaffolds and human articular chondrocytes.

Adult cartilage tissue has poor capability of self-repair, especially in case of severe cartilage damage due to trauma or age-related degeneration. Autologous cell-based tissue engineering using three-dimensional (3-D) porous scaffolds has provided an option for the repair of full thickness defects in adult cartilage tissue. Mesenchymal stem cells (MSCs) and chondrocytes are the two major cell sources for cartilage tissue engineering. Silk fibroin as a naturally occurring degradable fibrous protein with unique mechanical properties, excellent biocompatibility and process-ability has demonstrated strong potential for skeletal tissue engineering. The present study combined adult human chondrocytes (hCHs) with aqueous-derived porous silk fibroin scaffolds for in vitro cartilage tissue engineering. The results were compared with a previous study using the same scaffolds but using MSCs to generate the cartilage tissue outcomes. Culture-expanded hCHs attached to, proliferated and re-differentiated in the scaffolds in a serum-free, chemically defined medium containing TGF-beta1, based on cell morphology, levels of cartilage-related gene transcripts, and the presence of a cartilage-specific ECM. Cell density was critical for the redifferentiation of culture-expanded hCHs in the 3-D aqueous-derived silk fibroin scaffolds. The level of cartilage-related transcripts (AGC, Col-II, Sox 9 and Col-II/Col-I ratio) and the deposition of cartilage-specific ECM were significantly upregulated in constructs initiated with higher seeding density. The hCH-based constructs were significantly different than those formed from MSC-based constructs with respect to cell morphology, zonal structure and initial seeding density needed to successfully generate engineered cartilage-like tissue. These results suggest fundamental differences between stem cell-based (MSC) and primary cell-based (hCH) tissue engineering, as well as the importance of suitable scaffold features, in the optimization of cartilage-related outcomes in vitro. The present work diversifies cell sources in combination with silk fibroin-based tissue engineering applications. Together with our previous studies, the present results show great promise for engineered 3-D silk fibroin scaffolds in autologous cell-based skeletal tissue engineering.

Animals↗

PubMed2006

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial.

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups. CONCLUSIONS: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.

Adult↗

PubMed2006

Expansion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells on a vitamin C functionalized polymer.

In human body ascorbic acid plays an essential role in the synthesis and function of skeletal tissues and immune system factors. Ascorbic acid is also a major physiological antioxidant, repairing oxidatively damaged biomolecules, preventing the formation of excessive reactive oxygen species or scavenging these species. We recently reported the synthesis of ascorbic acid-functionalized polymers in which the antioxidant features of the pendant ascorbic acid groups was preserved. In the present work we demonstrate that ascorbic acid-functionalized poly(methyl methacrylate) (AA-PMMA) can modulate the proliferation and osteogenic differentiation of early and late-passage bone marrow-derived human mesenchymal stem cells (MSCs). The covalently coupled ascorbic acid impacted MSCs differently than when ascorbic acid was presented to the cells in soluble form. At optimal concentration, the covalently coupled ascorbic acid and soluble ascorbic acid synergistically promoted and retained the ability of MSCs to respond to osteogenic stimulation over extensive cell expansions in vitro. In the presence of soluble ascorbic acid, AA-PMMA films prepared at optimal concentrations (0.1 mg/ml in the present study) showed a significant promotive effect over other concentrations and tissue culture plastic (TCP) with respect to osteogenic differentiation of both EP (young) and LP (old) MSCs. These results suggest that the coupled ascorbic acid is acting mainly at the extracellular level and, at optimal concentrations, the immobilized extracellular ascorbic acid and soluble ascorbic acid synergistically promote osteogenic differentiation of MSCs. Importantly, the covalently coupled ascorbic acid on the films of optimal concentration was able to preserve the capacity of MSCs to undergo osteogenic differentiation in vitro. These results suggest an important role for functionalized biomaterials with antioxidant features in control of cell physiology and cell aging phenomena.

Aging↗

PubMed2006

Regulatory T cells induced by rAAV carrying the forkhead box P3 gene prevent autoimmune thyroiditis in mice.

CD4+CD25+ regulatory T (Treg) cells are immunosuppressive and help maintain peripheral immune tolerance. The forkhead/winged helix family member, Foxp3, has been shown to be a critical regulator of CD4+CD25+ Treg cells. We demonstrate by quantitative real-time PCR that CD4+CD25+ T cells express higher levels of Foxp3 mRNA than other T cell populations. Recombinant adeno-associated virus vector carrying mouse Foxp3 gene under the control of the CMV promoter was generated and used to transduce CD4+CD25- T cells. These Foxp3-transduced T cells are similar to naturally occurring CD4+CD25+ regulatory T cells which show anergy and immunosuppressive activity in vitro. Furthermore, these Foxp3-transduced T cells prevent autoimmune thyroiditis transferred by pathogenic T cells in vivo. Our data indicates that Foxp3-transduced CD4+CD25- T cells may open new therapeutic strategies for immune disorders.

Animals↗

PubMed2005

In-stent neo-intimal hyperplasia after stem cell mobilization by granulocyte-colony stimulating factor Preliminary intracoronary ultrasound results from a double-blind randomized placebo-controlled study of patients treated with percutaneous coronary intervention for ST-elevation myocardial infarction (STEMMI Trial).

OBJECTIVE: The influence of treatment with granulocyte-colony stimulating factor (G-CSF) on the development of in-stent intimal hyperplasia is not known. We aimed to study this phenomenon in patients who had stents implanted in the course of an acute ST-elevation infarction and successively were treated with G-CSF. METHOD: We performed angiography and intracoronary ultrasound follow-up after 5 months in 41 consecutive patients in the STEMMI trial, which is a randomized double-blind placebo-controlled study on the effect of G-CSF injections on the myocardial function following acute myocardial infarction in patients treated with primary percutaneous coronary stent implantation. The intracoronary ultrasound images were analyzed by a blinded and independent core laboratory. RESULTS: There were no differences in in-stent neo-intimal hyperplasia determined by intracoronary ultrasound between patients treated with G-CSF compared to patients treated with placebo. Neo-intimal hyperplasia per mm of stent was 1.87 (+/-1.41) and 1.89 (+/-1.39), respectively (p = 0.97). Angiographic in-segment restenosis (>50% diameter stenosis) was found in 28% of patients (24% in the G-CSF group and 33% in the placebo group; p = 0.55). CONCLUSION: G-CSF treatment following coronary stent implantation in primary PCI treated AMI patients does not increase in-stent restenosis excessively and it does not seem warranted to limit further study of effects of G-CSF for that reason.

Angioplasty, Balloon, Coronary↗

PubMed2005

Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease.

OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were "poor mobilizers" with a maximal increase in CD34+ cells to 5,000+/-700/mL blood (mean+/-S.D.) compared to 28,900+/-5,100/mL blood in "mobilizers". At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in "mobilizers" compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% (p<0.01, MRI) and from 48% to 44% (p=0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. CONCLUSIONS: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded.

Aged↗

PubMed2005

In vitro degradation of silk fibroin.

A significant need exists for long-term degradable biomaterials which can slowly and predictably transfer a load-bearing burden to developing biological tissue. In this study Bombyx mori silk fibroin yarns were incubated in 1mg/ml Protease XIV at 37 degrees C to create an in vitro model system of proteolytic degradation. Samples were harvested at designated time points up to 12 weeks and (1) prepared for scanning electron microscopy (SEM), (2) lyophilized and weighed, (3) mechanical properties determined using a servohydraulic Instron 8511, (4) dissolved and run on a SDS-PAGE gel, and (5) characterized with Fourier transform infrared spectroscopy. Control samples were incubated in phosphate-buffered saline. Fibroin was shown to proteolytically degrade with predictable rates of change in fibroin diameter, failure strength, cycles to failure, and mass. SEM indicated increasing fragmentation of individual fibroin filaments from protease-digested samples with time of exposure to the enzyme; particulate debris was present within 7 days of incubation. Gel electrophoresis indicated a decreasing amount of the silk 25 kDa light chain and a shift in the molecular weight of the heavy chain with increasing incubation time in protease. Results support that silk is a mechanically robust biomaterial with predictable long-term degradation characteristics.

Absorbable Implants↗

PubMed2005

In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells.

Adult cartilage tissue has limited self-repair capacity, especially in the case of severe damages caused by developmental abnormalities, trauma, or aging-related degeneration like osteoarthritis. Adult mesenchymal stem cells (MSCs) have the potential to differentiate into cells of different lineages including bone, cartilage, and fat. In vitro cartilage tissue engineering using autologous MSCs and three-dimensional (3-D) porous scaffolds has the potential for the successful repair of severe cartilage damage. Ideally, scaffolds designed for cartilage tissue engineering should have optimal structural and mechanical properties, excellent biocompatibility, controlled degradation rate, and good handling characteristics. In the present work, a novel, highly porous silk scaffold was developed by an aqueous process according to these criteria and subsequently combined with MSCs for in vitro cartilage tissue engineering. Chondrogenesis of MSCs in the silk scaffold was evident by real-time RT-PCR analysis for cartilage-specific ECM gene markers, histological and immunohistochemical evaluations of cartilage-specific ECM components. Dexamethasone and TGF-beta3 were essential for the survival, proliferation and chondrogenesis of MSCs in the silk scaffolds. The attachment, proliferation, and differentiation of MSCs in the silk scaffold showed unique characteristics. After 3 weeks of cultivation, the spatial cell arrangement and the collagen type-II distribution in the MSCs-silk scaffold constructs resembles those in native articular cartilage tissue, suggesting promise for these novel 3-D degradable silk-based scaffolds in MSC-based cartilage repair. Further in vivo evaluation is necessary to fully recognize the clinical relevance of these observations.

Adult↗

PubMed2004

Resonance Rayleigh scattering study of the reaction of nucleic acids with thionine and its analytical application.

Resonance Rayleigh scattering (RRS) of the thionine (TH)-nucleic acids system and its analytical application have been studied. In pH 2.2 acidic buffer medium, some nucleic acids can react with TH to form TH-nucleic acids complex. This results in a great enhancement of RRS and the appearance of new RRS spectra. The RRS spectral characteristics of TH-ctDNA system, the affecting factors and the optimum conditions of the reaction have been investigated. The enhancement of the RRS signal is directly proportional to the concentration of nucleic acids in the range 0-10.0 microg/ml for calf thymus DNA and 0-15.0 microg/ml for yeast RNA, and its detection limits (3sigma) are 3.5 ng/ml for calf thymus DNA and 4.9 ng/ml for yeast RNA, respectively. The method shows a wide linear range and high sensitivity, and was applied to the determination of trace amounts of nucleic acid in synthetic samples and practical samples with satisfactory results. The bind properties for the interactions of TH with ctDNA were investigated using a Scatchard plot based on the measurement of the enhanced RRS data at 340 nm, and the binding number and intrinsic binding constant are 4.9 and 2.6 x 10(5) mol/dm(3), respectively.

Calibration↗

PubMed2002

Coronary bypass revascularization with radial artery and internal mammary artery grafts.

OBJECTIVE: To evaluate radial artery (RA) and internal mammary artery (IMA) grafts in coronary artery bypass and the use of color Doppler ultrasound in the peri-operative evaluation of IMA and radial-ulnar collateral circulation. METHODS: From June 1998 to June 2000, sixty cases of coronary bypass revascularization with RA and IMA were performed. Preoperatively, the radial-ulnar collateral circulation was evaluated with the modified Allen's test, color Doppler ultrasound and noninvasive oxygen saturation measurement. The IMA lumen and blood flow were measured at the first intercostal space with color Doppler ultrasound preoperatively and postoperatively. RESULTS: One patient (1.7%) died of serious cardiac arrhythmia on the fourth postoperative day. There were no arterial graft harvest related complications. Before harvesting, the ulnar artery blood flow was 30.78 +/- 9.71 ml/min, and it increased to 43.36 +/- 13.98 ml/min (40.87% increase, P < 0.01) after the operation. Compared with the baseline, there was no obvious change of IMA blood flow postoperatively (P > 0.05), but the systolic/diastolic flow ratio markedly decreased from 8.57 +/- 3.98 ml/min to 3.41 +/- 4.87 ml/min (P < 0.01). CONCLUSIONS: Arterial grafts can be safely used for coronary bypass revascularization with good results. The ulnar artery blood flow can increase compensatively after RA harvesting. The diastolic blood flow of grafted IMA markedly increased postoperatively. Color Doppler ultrasound was very helpful both in evaluating the radial-ulnar collateral circulation before RA harvesting and in assessing the patency of the grafted IMA after coronary artery bypass grafting (CABG).

Adult↗

PubMed2002

[Genotyping of hepatitis B virus and clinical investigation].

OBJECTIVE: To investigate the distribution of HBV genotypes in Changzhou area and to clarify the genotype-related difference in the liver function, the level of HBV DNA and the long-term effect of lamivudine in the pathogenicity of HBV. METHODS: Nested PCR and sequence analysis were conducted in 14 acute hepatitis (AH), 104 chronic hepatitis (CH), and 28 liver cirrhosis or hepatocellular carcinoma (LC/HCC) patients. RESULTS: One hundred and forty six samples were positive for HBV DNA, and 51 samples were classified as genotype B (34.9%), 95 samples were classified as genotype C, serum ALT value was 383.8 +/- 335.7 IU in patients with HBV genotypes B, and 364.3 +/- 333.7 IU in genotypes C, HBV DNA value was 10(7.795 +/- 1.22) copies/ml in genotypes B and 10(7.69 +/0- 1.19) copies/ml in genotypes C, and there were 36 and 64 HBeAg positive cases in patients with genotypes B and C; there were no significant difference on the level of ALT, HBV DNA and the expression of HBeAg (P>0.05), but genotype C in LC/HCC was higher than CH (P<0.01). Twenty three genotype B and forty five genotype C patients received lamivudine treatment, after 48 weeks, 18 genotype B and 14 genotype C patients had higher ALT or HBV DNA positive. CONCLUSIONS: These results indicate that genotype B and C existing Changzhou area; genotype C is associated with the development of severe liver disease and better therapeutic effect could be obtained in the patients with genotype C.

Adult↗

PubMedDate not supplied

Myocardial gene expression of angiogenic factors in human chronic ischemic myocardium: influence of acute ischemia/cardioplegia and reperfusion.

OBJECTIVE: Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression. METHODS: Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors. RESULTS: There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium. CONCLUSION: These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium.

Aged↗