A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. Abdominal aortic aneurysm (AAA) is a major pathological condition because it affects approximately 8% of elderly men and 1.5% of elderly women. The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases. The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes.
- Klíčová slova
- ECM, VSMCs, inflammation, vessel,
- MeSH
- aneurysma břišní aorty * metabolismus MeSH
- aorta metabolismus MeSH
- apoptóza genetika MeSH
- cytokiny metabolismus MeSH
- fenotyp MeSH
- lidé MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- cytokiny MeSH
It is now widely recognized that mesenchymal stem cells (MSCs) possess the capacity to differentiate into a wide array of cell types. Numerous studies have identified the role of lncRNA in the regulation of MSC differentiation. It is important to elucidate the role and interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of signalling pathways that govern MSC function. Furthermore, miRNAs and lncRNAs are important clinical for innovative strategies aimed at addressing a wide spectrum of existing and emerging disease. Hence it is important to consider their impact on MSC function and differentiation. Examining the data available in public databases, we have collected the literature containing the latest discoveries pertaining to human stem cells and their potential in both fundamental research and clinical applications. Furthermore, we have compiled completed clinical studies that revolve around the application of MSCs, shedding light on the opportunities presented by harnessing the regulatory potential of miRNAs and lncRNAs. This exploration of the therapeutic possibilities offered by miRNAs and lncRNAs within MSCs unveils exciting prospects for the development of precision therapies and personalized treatment approaches. Ultimately, these advancements promise to augment the efficacy of regenerative strategies and produce positive outcomes for patients. As research in this field continues to evolve, it is imperative to explore and exploit the vast potential of miRNAs and lncRNAs as therapeutic agents. The findings provide a solid basis for ongoing investigations, fuelling the quest to fully unlock the regenerative potential of MSCs.
- Klíčová slova
- lncRNA, mesenchymal stem cells, miRNA,
- MeSH
- buněčná diferenciace genetika MeSH
- lidé MeSH
- mezenchymální kmenové buňky * metabolismus MeSH
- mikro RNA * genetika metabolismus MeSH
- osteoblasty metabolismus MeSH
- RNA dlouhá nekódující * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA * MeSH
- RNA dlouhá nekódující * MeSH
Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers-CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton's jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.
- Klíčová slova
- MSC, RNAseq, Wharton’s jelly, apoptosis, differentiation, mesenchymal stem cells,
- MeSH
- apoptóza genetika MeSH
- buněčná diferenciace genetika MeSH
- chondrocyty MeSH
- kultivované buňky MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- osteoblasty MeSH
- proteiny nervové tkáně MeSH
- transkriptom MeSH
- tukové buňky MeSH
- Whartonův rosol * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BEX2 protein, human MeSH Prohlížeč
- proteiny nervové tkáně MeSH
Heart failure remains a major cause of death worldwide. There is a need to establish new management options as current treatment is frequently suboptimal. Clinical approaches based on autologous stem cell transplant is potentially a good alternative. The heart was long considered an organ unable to regenerate and renew. However, several reports imply that it may possess modest intrinsic regenerative potential. To allow for detailed characterization of cell cultures, whole transcriptome profiling was performed after 0, 7, 15, and 30 days of in vitro cell cultures (IVC) from the right atrial appendage and right atrial wall utilizing microarray technology. In total, 4239 differentially expressed genes (DEGs) with ratio > abs |2| and adjusted p-value ≤ 0.05 for the right atrial wall and 4662 DEGs for the right atrial appendage were identified. It was shown that a subset of DEGs, which have demonstrated some regulation of expression levels with the duration of the cell culture, were enriched in the following GO BP (Gene Ontology Biological Process) terms: "stem cell population maintenance" and "stem cell proliferation". The results were validated by RT-qPCR. The establishment and detailed characterization of in vitro culture of myocardial cells may be important for future applications of these cells in heart regeneration processes.
- Klíčová slova
- cardiomyocytes, long-term in vitro cell culture, porcine cardiac muscle, stemness markers, transcriptomic analysis,
- MeSH
- buněčné kultury MeSH
- kardiomyocyty * metabolismus MeSH
- prasata MeSH
- regulace genové exprese * MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40-160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.
- Klíčová slova
- cancer, cancer therapies, drug resistance, exosomes,
- MeSH
- exozómy * fyziologie MeSH
- karcinogeneze MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- nádory * patologie MeSH
- nosiče léků terapeutické užití MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- nosiče léků MeSH
Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton's jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton's jelly, is a promising source of mesenchymal stem cells.
- Klíčová slova
- Wharton’s jelly, stem cells, umbilical cord,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The repair of bone defects caused by trauma, infection or tumor resection is a major clinical orthopedic challenge. The application of bone grafts in orthopedic procedures is associated with a problem of inadequate vascularization in the initial phase after implantation. Meanwhile, the survival of cells within the implanted graft and its integration with the host tissue is strongly dependent on nutrient and gaseous exchange, as well as waste product removal, which are effectuated by blood microcirculation. In the bone tissue, the vasculature also delivers the calcium and phosphate indispensable for the mineralization process. The critical role of vascularization for bone healing and function, led the researchers to the idea of generating a capillary-like network within the bone graft in vitro, which could allow increasing the cell survival and graft integration with a host tissue. New strategies for engineering pre-vascularized bone grafts, that apply the co-culture of endothelial and bone-forming cells, have recently gained interest. However, engineering of metabolically active graft, containing two types of cells requires deep understanding of the underlying mechanisms of interaction between these cells. The present review focuses on the best-characterized endothelial cells-human umbilical vein endothelial cells (HUVECs)-attempting to estimate whether the co-culture approach, using these cells, could bring us closer to development and possible clinical application of prevascularized bone grafts.
- Klíčová slova
- and prevascularization, co-culture, human umbilical vein endothelial cells, mesenchymal stem cells, osteoblasts,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Coronary artery bypass grafting (CABG) is one of the most efficient procedures for patients with advanced coronary artery disease. From all the blood vessels with the potential to be used in this procedure, the internal thoracic artery (ITA) and the saphenous vein (SV) are the most commonly applied as aortocoronary conduits. Nevertheless, in order to evaluate the graft patency and efficiency effectively, basic knowledge should be constantly expanding at the molecular level as well, as the understanding of predictive factors is still limited. In this study, we have employed the expressive microarray approach, validated with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), to analyze the transcriptome of both venous and arterial grafts. Searching for potential molecular factors, we analyzed differentially expressed gene ontologies involved in bone development and morphogenesis, for the possibility of discovery of new markers for the evaluation of ITA and SV segment quality. Among three ontological groups of interest-"endochondral bone morphogenesis", "ossification", and "skeletal system development"-we found six genes common to all of them. BMP6, SHOX2, COL13A1, CSGALNACT1, RUNX2, and STC1 showed differential expression patterns in both analyzed vessels. STC1 and COL13A1 were upregulated in ITA samples, whereas others were upregulated in SV. With regard to the Runx2 protein function in osteogenic phenotype regulation, the RUNX2 gene seems to be of paramount importance in assessing the potential of ITA, SV, and other vessels used in the CABG procedure. Overall, the presented study provided valuable insight into the molecular background of conduit characterization, and thus indicated genes that may be the target of subsequent studies, also at the protein level. Moreover, it has been suggested that RUNX2 may be recognized as a molecular marker of osteogenic changes in human blood vessels.
- Klíčová slova
- coronary artery bypass grafting, internal thoracic artery, osteogenesis, saphenous vein,
- MeSH
- aorta thoracica metabolismus MeSH
- biologické markery MeSH
- genové regulační sítě MeSH
- koronární bypass * MeSH
- lidé MeSH
- morfogeneze genetika MeSH
- stanovení celkové genové exprese MeSH
- vena saphena metabolismus MeSH
- výpočetní biologie metody MeSH
- vývoj kostí genetika MeSH
- vývojová regulace genové exprese * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
The growth and development of oocyte affect the functional activities of the surrounding somatic cells. These cells are regulated by various types of hormones, proteins, metabolites, and regulatory molecules through gap communication, ultimately leading to the development and maturation of oocytes. The close association between somatic cells and oocytes, which together form the cumulus-oocyte complexes (COCs), and their bi-directional communication are crucial for the acquisition of developmental competences by the oocyte. In this study, oocytes were extracted from the ovaries obtained from crossbred landrace gilts and subjected to in vitro maturation. RNA isolated from those oocytes was used for the subsequent microarray analysis. The data obtained shows, for the first time, variable levels of gene expression (fold changes higher than |2| and adjusted p-value < 0.05) belonging to four ontological groups: regulation of cell proliferation (GO:0042127), regulation of cell migration (GO:0030334), and regulation of programmed cell death (GO:0043067) that can be used together as proliferation, migration or apoptosis markers. We have identified several genes of porcine oocytes (ID2, VEGFA, BTG2, ESR1, CCND2, EDNRA, ANGPTL4, TGFBR3, GJA1, LAMA2, KIT, TPM1, VCP, GRID2, MEF2C, RPS3A, PLD1, BTG3, CD47, MITF), whose expression after in vitro maturation (IVM) is downregulated with different degrees. Our results may be helpful in further elucidating the molecular basis and functional significance of a number of gene markers associated with the processes of migration, proliferation and angiogenesis occurring in COCs.
- Klíčová slova
- cellular competence, microarray, oocytes, pig,
- MeSH
- apoptóza genetika MeSH
- down regulace MeSH
- genové regulační sítě MeSH
- IVM techniky MeSH
- kumulární buňky metabolismus patologie MeSH
- oocyty růst a vývoj metabolismus patologie MeSH
- pohyb buněk genetika MeSH
- prasata MeSH
- proliferace buněk genetika MeSH
- RNA genetika metabolismus MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- RNA MeSH