Objective To explore the feasibility of tissue-engineered heart valve （TEHV） reconstructed on acellularized porcine aortic valve and rabbit bone marrow stromal cells （BMSCs） in vitro. Methods Acellularized was performed in porcine aortic valve by the detergent and enzymatic extraction process . Morphological and biomechanical properties were compared between the decellularized scaffolds and the fresh valves. Rabbit BMSCs were seeded on the scaffolds. The TEHV were analyzed by light microscopy, electron microscopy and immunohistochemistry. Results Almost complete removal of the cellular components and soluble protein of valves were observed , while the construction of matrix was properly maintained. Biomechanical tests demonstrated no statistically significant change in the breaking intensity （642 ± 102 g/mm2 vs. 636 ± 127g/mm2） and breaking extensibility （62. 2%± 18. 1% vs. 54. 4%±16. 0%） in the porcine values before and after decellularization. Subsequent seeding with rabbit BMSCs on the matrix was so successful that the surface of the scaffold had been covered with a continuous monolayer cells through light microscopy and electron microscopy. Positive of α-smooth muscle actin and negative of CD31 were observed after rabbit BMSCs seeded on the matrix through immunohistochemistry. Conclusion It is feasible to reconstruct TEHV in vitro on acellularized porcine aortic valve scaffold and rabbit BMSCs.
The engineered heart tissues (EHTs) present a promising alternative to current materials for native myocardial tissue due to the unique characteristics. However, until now, the clinical application of EHTs is limited by a serial of practical problems yet. Generally, the challenges need to further optimize include biomaterials, cell sources, and strategies of revascularization or establishment of EHTs. This review focuses on the newly progress on these aspects to encourage the emergence of novel EHTs that can meet clinic requirement properly.
Objective To investigate the experience of left ventricular reconstruction（LVR）in a rat model with post-infarction ventricular aneurysm. Methods A total of 35 male Sprague-Dawley （SD）rats underwent left anterior descending artery （LAD） ligation to create a left ventricular aneurysm （LVA) model following myocardial infarction. Four weeks later, 16 rats with LVA that met the inclusion criteria underwent LVR as the experiment group（LVR group）. Another 10 rats with LVA underwent thoracotomy as the control group. Three days, 2 weeks, and 4 weeks after the second operation, all the rats were examined by echocardiography to evaluate the cardiac function. At the end of the study, photography and Masson’s Trichrome staining were used to evaluate the completeness of LVA resection. Results The surgical mortality of LVA and LVR generation was 11.4%（4/35）and 18.8%（3/16）respectively， with the success rate 74.3% （26/35）for LVA model and 81.3%（13/16）for LVR model. Photography and Masson’s Trichrome staining identified complete replacement of ventricular scar by patch. Three days after the second operation, echocardiography illustrated that the left ventricular end-systolic diameter （LVESD）and fractional shortening （FS） of the LVR group were significantly improved compared with the control group （LVESD 5.00±0.87 mm versus 5.90±0.92 mm, P＜0.05，FS 34.20%± 6.80% versus 26.60%±6.12%, P＜ 0.01）. The cardiac structure and function of LVR group were also significantly improved 2 weeks and 4 weeks after the second operation compared with the control group（2 weeks：left ventricular end-diastolic diameter （LVEDD）7.60±0.56 mm versus 8.50±1.08 mm，P＜ 0.01；LVESD 5.10±0.65 mm versus 6.69±0.89 mm，P＜0.001；FS 31.90%±6.90% versus 21.10%±6.17%，P＜0.001；4 weeks：LVEDD7.70±0.50 mm versus 9.10±0.89 mm，P＜0.001；LVESD5.20±0.39 mm versus 7.20±0.95 mm，P＜0.001；FS 31.80%±2.40% versus 20.20%±4.17%，P＜0.001）. Conclusions LVR rat can be used as a stable, reliable and economic screeningmodel in engineered heart tissue（EHT）research.
The engineered heart tissues (EHTs) is regarded as a hope for myocardial repair and regeneration. But a series of " bottleneck” problems, such as vascularization, hinder their clinical translation. This review focuses on the strategies to vascularization of EHTs and encourages the emergence of novel EHTs that can meet clinic requirement properly.
With the development of molecular and cellar cardiology, gene therapy to cardiovascular disease has become the hot spot and the direction of study. Now, preclinical studies on ultrasound-mediated gene delivery (UMGD) in cardiovascular disease have achieved some success, but it is still hindered by a series of practical challenges for clinical translation. Even so, UMGD still holds the promise to cardiovascular disease in gene therapy for its non-invasiveness, accuracy, safety and ability to deliver multiple genes with repeated deliveries. In this review, we will focus on the basic principle, the current development, the future prospect and drawbacks of UMGD in the therapeutic applications of cardiovascular disease.
ObjectiveTo investigate the feasibility of animal model of the reconstruction of right ventricular outflow tract in rats.MethodsA total of 15 female Sprague-Dawley (SD) rats underwent right ventricular outflow tract reconstruction surgery. Before the operation, the collagen scaffolds were treated with g 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride chemistry (EDC), and seeded with human bone marrow stem cells (h-MSCs). Three days after the surgery, 3 rats were randomly sacrificed to evaluate the transmural resection of right ventricular outflow tract. One or 3 months later, other 3 rats at each timepoint were sacrificed, stained with Masson’s Trichrome to observe the degradation of scaffold. Furthermore, 4 weeks after the surgery, 4 rats were sacrificed and the hearts were sliced. Anti-human mitochondria staining was used to identify the survival of seeding cells.ResultsThe transmural resection of right ventricular outflow tract was feasible in rats at an acceptable mortality (13.3%). After EDC treatment, the degradation rate of collagen scaffold was extended greatly. The seeding cells were detected by anti-mitochandria immunofluorescent staining in all patches 4 weeks after the operation.ConclusionRat model of right ventricular outflow tract reconstruction could be a stable, reliable and economical screening model for engineered heart tissue research.
ObjectiveTo compare the anti-apoptotic potency of human mesenchymal stem cells (hMSCs) derived from patients with cyanotic congenital heart diseases (C-CHD) or acyanotic congenital heart diseases (A-CHD) in vitro and explore the possible mechanism. MethodshMSCs were isolated from patients with cyanotic (Group C) or acyanotic (Group A) congenital heart diseases and cultured in a hypoxic incubator (1% O2, 5% CO2, 94% N2) in vitro. The anti-apoptotic potency of the hMSCs was assayed by the Annexin V-FITC/PI double labeled flow cytometry. The content of B-cell lymphoma-2 (Bcl-2), Bax and caspase-3 in both groups was determined by Western blot. ResultsFlow cytometry results revealed that hMSCs from C-CHD patients presented higher level of resistance to ischemia-and anoxia-induced apoptosis with lower overall (P<0.05) and early apoptosis ratio (P<0.01). Further Western blot examination identified that C-CHD-derived hMSCs produced more Bcl-2 (P<0.05) but less Bax (P<0.05) and caspase-3 (P<0.05) in comparison to their A-CHD-derived ones. ConclusionC-CHD-derived hMSCs presented the superiority for the anti-apoptotic potential, and the possible mechanism is the favorable change of Bcl-2, Bax and caspase-3 induced by the natural hypoxic and anoxic precondition.