Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.
Black phosphorene has attracted much attention as a semiconducting two‐dimensional material. Violet phosphorus is another layered semiconducting phosphorus allotrope with unique electronic and optoelectronic properties. However, no confirmed violet crystals or reliable lattice structure of violet phosphorus had been obtained. Now, violet phosphorus single crystals were produced and the lattice structure has been obtained by single‐crystal x‐ray diffraction to be monoclinic with space group of P2/n (13) (a=9.210, b=9.128, c=21.893 Å, β=97.776°). The lattice structure obtained was confirmed to be reliable and stable. The optical band gap of violet phosphorus is around 1.7 eV, which is slightly larger than the calculated value. The thermal decomposition temperature was 52 °C higher than its black phosphorus counterpart, which was assumed to be the most stable form. Violet phosphorene was easily obtained by both mechanical and solution exfoliation under ambient conditions.
Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types.
Rationale
Stem cell therapy faces a number of challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine.
Objective
We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice.
Methods and Results
We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into Poly(lactic-co-glycolic acid) PLGA microparticles and then coated them with MSC membranes. We named these therapeutic particles “synthetic MSC” (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling.
Conclusions
We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
Stem
cell transplantation is currently implemented clinically but
is limited by low retention and engraftment of transplanted cells
and the adverse effects of inflammation and immunoreaction when allogeneic
or xenogeneic cells are used. Here, we demonstrate the safety and
efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive
poly(N-isopropylacrylamine-co-acrylic
acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial
infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection
of nanogel-encapsulated hCSCs does not elicit systemic inflammation
or local T cell infiltrations in immunocompetent mice. In mice and
pigs with acute MI, injection of encapsulated hCSCs preserves cardiac
function and reduces scar sizes, whereas injection of hCSCs in saline
has an adverse effect on heart healing. In conclusion, thermosensitive
nanogels can be used as a stem cell carrier: the porous and convoluted
inner structure allows nutrient, oxygen, and secretion diffusion but
can prevent the stem cells from being attacked by immune cells.
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