Cardiac matrix hydrogel has shown great promise as an injectable biomaterial due to the possession of cardiac-specific extracellular matrix composition. A cardiac matrix hydrogel facilitating neovascularization will further improve its therapeutic outcomes in cardiac repair. In this study, we explored the feasibility of tailoring material properties of cardiac matrix hydrogels using a natural compound, genipin, to promote endothelial differentiation of stem cells. Our results demonstrated that the genipin crosslinking could increase the mechanical properties of the cardiac matrix hydrogel to a stiffness range promoting endothelial differentiation of human mesenchymal stem cells (hMSCs). It also decreased the swelling ratio and prolonged degradation without altering gelation time. Human mesenchymal stem cells cultured on the genipin crosslinked cardiac matrix hydrogels showed great viability. After 1-day culture, hMSCs demonstrated downregulation of early endothelial marker expression and up-regulation of mature endothelial marker expression. Especially for 1 mM genipin crosslinked cardiac matrix hydrogels, hMSCs showed particularly significant expression of mature endothelial cell marker vWF. These attractive results indicate the potential of using genipin crosslinked cardiac matrix hydrogels to promote rapid vascularization for cardiac infarction treatment through minimally invasive therapy.

Prevacularization strategies have been implemented in tissue engineering to generate microvasculature networks within a scaffold prior to implantation. Prevascularizing scaffolds will shorten the time of functional vascular perfusion with host upon implantation. In this study, we explored key variables affecting the interaction between decellularized porcine myocardium slices (dPMSs) and reseeded stem cells toward the fabrication of prevascularized cardiac tissue. Our results demonstrated that dPMS supports attachment of human mesenchymal stem cells (hMSCs) and rat adipose derived stem cells (rASCs) with high viability. We found that cell seeding efficiency and proliferation are dPMS thickness dependent. Compared to lateral cell seeding, bilateral cell seeding strategy significantly enhanced seeding efficiency, infiltration, and growth in 600 μm dPMS. dPMS induced endothelial differentiation and maturation of hMSCs and rASCs after 1 and 5 days culture, respectively. These results indicate the potential of dPMS as a powerful platform to develop prevascularized scaffolds and fabricate functional cardiac patches.

Decellularized porcine myocardium has shown many benefits as a cell delivery scaffold for cardiac therapy. However, using full thickness decellularized myocardium as cardiac patch may lead to poor viability and inhomogeneous distribution of delivered cells, due to perfusion limitations. In this study, we explored the feasibility of decellularized porcine myocardial slice (dPMS) to construct a vascularized cardiac patch for cell delivery. Decellularized porcine myocardium was sliced into thin layers (thickness~300 µm). Adipose-derived Stem cells (ASCs) obtained from rat and pig were seeded on dPMS. The viability, infiltration, and differentiation of seeded ASCs were examined. The mechanical properties of dPMSs of various thickness and native myocardium were tested. We noticed dPMS supported attachment and growth of rat and pig ASCs. Both rat and pig ASCs showed high viability, similar patterns of proliferation and infiltration within dPMS. Rat ASCs showed expression of early-endothelial markers followed by mature-endothelial marker without any additional inducers on dPMS. Using rat myocardial infarction model, we delivered ASCs using dPMS patched to the infarcted myocardium. After 1 week, a higher number of transplanted cells were present in the infarcted area when cells were delivered using dPMS versus direct injection. Compared with MI group, increased vascular formation was also observed.

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Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding the cell degeneration and apoptosis mechanism.

Acellular cardiac patches made of various biomaterials have shown to improve heart function after myocardial infarction (MI). Extracellular matrix scaffold derived from a decellularized tissue has unique advantages to serve as an acellular cardiac patch due to its biomimetic nature. In this study, we examined the therapeutic outcomes of using a decellularized porcine myocardium slice (dPMS) as an acellular patch in a rat acute MI model. dPMSs with two different thicknesses (300 and 600 μm) were patched to the infarcted area of the rat myocardium, and their effects on cardiac function and host interactions were assessed. We found that the implanted dPMS firmly attached to host myocardium after implantation and prevented thinning of the left ventricular (LV) wall after an MI. A large number of host cells were identified to infiltrate into the implanted dPMS, and a significant number of vessel structures was observed in the dPMS and infarcted area. We detected a significantly higher density of M2 macrophages in the groups treated with dPMSs as compared to the MI group. Contraction of the LV wall and cardiac functional parameters (left ventricular ejection fraction and fractional shortening) was significantly improved in the treatment groups (300 and 600 μm dPMS) 4 weeks after surgery. Our results proved the therapeutic benefits of using dPMS as an acellular cardiac patch for the treatment of acute myocardial infarction.

Dedifferentiated fat cells show great promises as a novel cell source for stem cell research. It has many advantages when used for cell-based therapeutics including abundance, pluripotency, and safety. However, there are many obstacles researchers need to overcome to make the next big move in DFAT cells research. In this review, we summarize the current main challenges in DFAT cells research including cell culture purity, phenotypic properties, and dedifferentiation mechanisms. The common methods to produce DFAT cells as well as the cell purity issue during DFAT cell production have been introduced. Current approaches to improve DFAT cell purity have been discussed. The phenotypic profile of DFAT cells have been listed and compared with other stem cells. Further studies on elucidating the underlying dedifferentiation mechanisms will dramatically advance DFAT cell research.

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