A Novel Conductive Polypyrrole-Chitosan Hydrogel Containing Human Endometrial Mesenchymal Stem Cell-Derived Exosomes Facilitated Sustained Release for Cardiac Repair.

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY-CHI/hEMSC-Exo, compared to untreated controls, PPY-CHI, or hEMSC-Exo alone, alleviates H2O2-induced apoptosis and promotes tubule formation, while in vivo, PPY-CHI/hEMSC-Exo improves post-MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3-kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY-CHI/hEMSC-Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY-CHI/hEMSC-Exo synergistically combines the cardiac regenerative capabilities of hEMSC-Exo with the conductive properties of PPY-CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long-term exosome release and sustained application of their beneficial effects.

Efficacy Evaluation and Tracking of Bone Marrow Stromal Stem Cells in a Rat Model of Renal Ischemia-Reperfusion Injury.

OBJECTIVES: The aim of this study was to evaluate the effects of bone marrow stromal stem cells (BMSCs) on renal ischemia-reperfusion injury (RIRI) and dynamically monitor engrafted BMSCs in vivo for the early prediction of their therapeutic effects in a rat model. METHODS: A rat model of RIRI was prepared by clamping the left renal artery for 45 min. One week after renal artery clamping, 2 × 106 superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected into the renal artery. Next, MR imaging of the kidneys was performed on days 1, 7, 14, and 21 after cell transplantation. On day 21, after transplantation, serum creatinine (Scr) and urea nitrogen (BUN) levels were assessed, and HE staining and TUNEL assay were also performed. RESULTS: The body weight growth rates in the SPIO-BMSC group were significantly higher than those in the PBS group (P < 0.05), and the Scr and BUN levels were also significantly lower than those in the PBS group (P < 0.05). HE staining showed that the degree of degeneration and vacuole-like changes in the renal tubular epithelial cells in the SPIO-BMSC group was significantly better than that observed in the PBS group. The TUNEL assay showed that the number of apoptotic renal tubular epithelial cells in the SPIO-BMSC group was significantly lower than that in the PBS group. The T2 value of the renal lesion was the highest on day 1 after cell transplantation, and it gradually decreased with time in both the PBS and SPIO-BMSC groups but was always the lowest in the SPIO-BMSC group. CONCLUSION: SPIO-labeled BMSC transplantation can significantly promote the recovery of RIRI and noninvasive dynamic monitoring of engrafted cells and can also be performed simultaneously with MRI in vivo for the early prediction of therapeutic effects.

FSCN1 is upregulated by SNAI2 and promotes epithelial to mesenchymal transition in head and neck squamous cell carcinoma.

In this study, we investigated whether there is any association between the expression of FSCN1 and SNAI2 and the possible underlying mechanisms in head and neck squamous cell carcinoma (HNSC). In addition, we also investigated whether FSCN1 modulates epithelial-to-mesenchymal transition (EMT) in HNSC cells. Microarray data of dysregulated genes in HNSC were searched in GEO datasets. The association between FSCN1 expression and the 5-year/10-year overall survival (OS), as well as the correlation between the expression of FSCN1 and SOX2, MYBL2, SNAI2, STAT1, and SOX4, was analyzed based on data in TCGA HNSC cohort (TCGA-HNSC). The binding site of SNAI2 in FSCN1 promoter was verified using luciferase reporter assay. SCC9 and SCC15 cells were transfected with pCMV-SNAI2 or pCMV-FSCN1 expression vector or the empty control. Alteration of E-cadherin, Claudin 1, Vimentin, and N-cadherin was then quantified. Our results showed that FSCN1 is significantly upregulated in HNSC tissues compared with the normal control tissues. High FSCN1 expression is associated with worse 5-year and 10-year OS among the HNSC patients. Bioinformatic prediction showed a highly possible SNAI2 binding site in FSCN1 promoter and following luciferase reporter assay verified this site. SNAI2 overexpression significantly increased FSCN1 expression at both mRNA and protein level. FSCN1 overexpression reduced the expression of E-cadherin and Claudin 1, but increased the expression of Vimentin and N-cadherin in SCC9 and SCC-15 cells. Therefore, we infer that FSCN1 is a downstream effector of SNAI2 in promoting EMT in HNSC cells.