Background Engineered heart tissues (EHTs) present a promising alternative to current materials for surgical ventricular restoration (SVR); however, the clinical application remains limited by inadequate vascularization postimplantation. Moreover, a suitable and economic animal model for primary screening is another important issue. Methods Recently, we used 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride chemistry (EDC) to initiate a strengthened, cytokine-conjugated collagenous platform with a controlled degradation speed. In vitro, the biomaterial exhibited an enhanced mechanical strength maintaining a porous ultrastructure, and the constant release of cytokines promoted the proliferation of seeded human mesenchymal stem cells (hMSCs). In vivo, with the hMSC-seeded, cytokine-immobilized patch (MSCs + GF patch), we performed modified SVR for rats with left ventricular aneurysm postmyocardial infarction (MI). Overall, the rats that underwent modified SVR lost less blood and had lower mortality. After 4 weeks, the rats repaired with this cell-seeded, cytokine-immobilized patch presented preserved cardiac function, beneficial morphology, enhanced cell infiltration, and functional vessel formation compared with the cytokine-free (MSC patch), cell-free (GF patch), or blank controls (EDC patch). Furthermore, the degradable period of the collagen patch in vivo extended up to 3 months after EDC treatment. Conclusions EDC may substantially modify collagen scaffold and provide a promising and practical biomaterial for SVR.
Allograft rejection is an important issue post cardiac transplantation. In order to investigate the effect of combined treatment with simvastatin and rapamycin on allograft rejection, a cardiac transplantation rat model was employed in the present study. The survival time of rats following cardiac transplantation was recorded, while histopathological alterations were assessed by hematoxylin and eosin staining. The levels of transcription factors were measured by reverse transcription-quantitative polymerase chain reaction. In addition, the levels of CD4+ interleukin (IL)-17+ cells and CD4+ forkhead box P3 (FOXP3)+ cells in the allografts and CD4+ T cells and CD8+ T cells in the spleens were detected by flow cytometry. The results of the current study demonstrated that, following treatment with simvastatin and rapamycin, the survival time of model rats was prolonged, and the histopathological damage was attenuated. Treatment with simvastatin and rapamycin also led to decreased retinoic acid receptor-related orphan receptor γt (RORγt) level, increased FOXP3 level, reduced levels of CD4+IL-17+, CD4+ T and CD8+ T cells, and increased level of CD4+FOXP3+ cells. In conclusion, the current study observed that simvastatin and rapamycin performed a synergistic effect to reduce cardiac transplantation rejection. Thus, combined therapy of simvastatin and rapamycin may be a promising adjuvant therapy to reduce rejection post cardiac transplantation.
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