This study aims to investigate the induction effect of LncRNA-CIR6 on MSC differentiation into cardiogenic cells in vitro and in vivo. In addition to pretreatment with Ro-3306 (a CDK1 inhibitor), LncRNA-CIR6 was transfected into BMSCs and hUCMSCs using jetPRIME. LncRNA-CIR6 was further transfected into the hearts of C57BL/6 mice via 100 μL of AAV9-cTnT-LncRNA-CIR6-ZsGreen intravenous injection. After three weeks of transfection followed by AMI surgery, hUCMSCs (5 × 10/100 μL) were injected intravenously one week later. Cardiac function was evaluated using VEVO 2100 and electric mapping nine days after cell injection. Immunofluorescence, Evans blue-TTC, Masson staining, FACS, and Western blotting were employed to determine relevant indicators. LncRNA-CIR6 induced a significant percentage of differentiation in BMSCs (83.00 ± 0.58)% and hUCMSCs (95.43 ± 2.13)% into cardiogenic cells, as determined by the expression of cTnT using immunofluorescence and FACS. High cTNT expression was observed in MSCs after transfection with LncRNA-CIR6 by Western blotting. Compared with the MI group, cardiac contraction and conduction function in MI hearts treated with LncRNA-CIR6 or combined with MSCs injection groups were significantly increased, and the areas of MI and fibrosis were significantly lower. The transcriptional expression region of LncRNA-CIR6 was on Chr17 from 80209290 to 80209536. The functional region of LncRNA-CIR6 was located at nucleotides 0-50/190-255 in the sequence. CDK1, a protein found to be related to the proliferation and differentiation of cardiomyocytes, was located in the functional region of the LncRNA-CIR6 secondary structure (from 0 to 17). Ro-3306 impeded the differentiation of MSCs into cardiogenic cells, while MSCs transfected with LncRNA-CIR6 showed a high expression of CDK1. LncRNA-CIR6 mediates the repair of infarcted hearts by inducing MSC differentiation into cardiogenic cells through CDK1.
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http://dx.doi.org/10.3390/ijms25063466 | DOI Listing |
ACS Omega
January 2025
Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, China.
The impact of changes in peripheral blood mononuclear cells (PBMCs) on the prognosis of patients with cardiogenic shock (CS) receiving venous-arterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. A single-cell RNA-sequencing (scRNA-seq) and a bulk RNA-sequencing (bulk RNA-seq) data sets of pre-ECMO PBMCs of CS patients were obtained from the gene expression omnibus database, which were analyzed using the "Seurat" and "limma" packages, respectively. The counts of different PMBC cell types, differential expression genes (DEGs), pathway enrichment analysis, cell-cell communication analysis, pseudotime analysis, and immune cell infiltration analysis were compared between VA-ECMO groups with different prognoses.
View Article and Find Full Text PDFDev Growth Differ
January 2025
Division of Anatomy and Developmental Biology, Department of Anatomy, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Sonic Hedgehog (Shh), encoding an extracellular signaling molecule, is vital for heart development. Shh null mutants show congenital heart disease due to left-right asymmetry defects stemming from functional anomaly in the midline structure in mice. Shh signaling is also known to affect cardiomyocyte differentiation, endocardium development, and heart morphogenesis, particularly in second heart field (SHF) cardiac progenitor cells that contribute to the right ventricle, outflow tract, and parts of the atrium.
View Article and Find Full Text PDFJ Pharm Biomed Anal
December 2024
Service of Clinical Pharmacology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Levosimendan is a positive inotrope and vasodilator used in patients with acute and chronic decompensated heart failure. It is metabolized into OR-1855 (inactive metabolite), which is further acetylated into OR-1896 (active metabolite having a prolonged half-life, hence a sustained effect). Levosimendan represents a valuable alternative to traditional inotropes with broad clinical applications in critically ill patients with cardiogenic shock, advanced heart failure and post-cardiac surgery.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biology, Indiana State University, Terre Haute, IN 47809, USA.
Cells
December 2024
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Heart disease, including myocardial infarction (MI), remains a leading cause of morbidity and mortality worldwide, necessitating the development of more effective regenerative therapies. Direct reprogramming of cardiomyocyte-like cells from resident fibroblasts offers a promising avenue for myocardial regeneration, but its efficiency and consistency in generating functional cardiomyocytes remain limited. Alternatively, reprogramming induced cardiac progenitor cells (iCPCs) could generate essential cardiac lineages, but existing methods often involve complex procedures.
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