These data raise a cautionary note on the therapeutic exploitation of cardiac stem cells in patients with ischemic cardiomyopathy, who may be the elective candidates for regenerative therapy.
Mechanobiology is a scientific interface discipline emerging from engineering and biology. With regard to tissue-regenerative cell-based strategies, mechanobiological concepts, including biomechanics as a target for cell and human mesenchymal stem cell behaviour, are on the march. Based on the periodontium as a paradigm, this mini-review discusses the key role of focal-adhesion kinase (FAK) in mechanobiology, since it is involved in mediating the transformation of environmental biomechanical signals into cell behavioural responses via mechanotransducing signalling cascades. These processes enable cells to adjust quickly to environmental cues, whereas adjustment itself relies on the specific intramolecular phosphorylation of FAK tyrosine residues and the multiple interactions of FAK with distinct partners. Furthermore, interaction-triggered mechanotransducing pathways govern the dynamics of focal adhesion sites and cell behaviour. Facets of behaviour not only include cell spreading and motility, but also proliferation, differentiation and apoptosis. In translational terms, identified and characterized biomechanical parameters can be incorporated into innovative concepts of cell- and tissue-tailored clinically applied biomaterials controlling cell behaviour as desired.
These data reveal that melatonin protects osteoblasts in the CHX context, thereby implicating melatonin as a promising drug in periodontitis and peri-implantitis treatment.
Various situations encountered by a clinician during the daily routine including surgical periodontitis therapy, dental implant insertion, or tooth extraction involve the contact of saliva with the jaw bone. However, there are only sparse data concerning the influence of saliva on bone cells. Saliva specimens were incorporated within culture medium and administered to murine MC3T3 osteoblasts, of which the morphology (REM), proliferation (EZ4U), and differentiation (qRT-PCR, alkaline phosphatase activity, extracellular matrix calcification) were assessed. Simultaneously, the composition of saliva media was analyzed with respect to the content of lactoferrin, activities of classical salivary enzymes, and the ability to provoke inflammatory cytokine production (enzyme-linked immunosorbent assay) in MC3T3 osteoblasts. The morphology, proliferation, and expression of differentiation-associated genes were seriously handicapped by saliva contact. Saliva-touched cells exhibited less alkaline phosphatase but normal levels of extracellular matrix mineralization. Saliva-containing culture media featured physiological activities of salivary enzymes and considerable amounts of lactoferrin but almost completely lacked salivary alkaline phosphatase and unspecific proteases. Upon saliva incubation, MC3T3 osteoblasts did not release noteworthy levels of interleukin-1 beta or tumor necrosis factor alpha. Although saliva is generally considered to vitalize oral tissues, this study reveals that it harms osteoblast-like cells more due to the presence of salivary enzymes than by triggering of inflammation. This issue is clinically relevant because it broadens the understanding of the bone cell fate within the rather complex cosmos of the oral cavity thereby providing a basis for clinical decision making and treatment guidelines. It seems to be reasonable to restrict the contact period between saliva and bone.
The limited plasticity of adult muscle- or bone marrow- derived stem cells intended for cardiac regeneration impedes their conversion into cardiomyocytes. Since murine skeletal muscle was reported to harbor cardiac precursor cells, we assessed whether similar cells exist in man. Skeletal muscle biopsies obtained from 39 patients were sorted by flow cytometry which generated three populations (CD90+/CD34(-), CD34+/CD90(-), CD90(-)/CD34(-)) expressing similar levels of cardiac (Nkx2.5, cTn-T, cTn-I, Cx43) and skeletal muscle (Myf-5, MyoD, myogenin) mRNAs, as assessed by quantitative reverse transcriptase-PCR. However, compared to unpurified myoblasts, CD34+/CD90(-) cells expressed greater amounts of endothelium-specific mRNAs and were, therefore, selected for transplantation experiments. Thirty immunosuppressed rats then underwent coronary artery ligation and, 4 weeks later, were intramyocardially injected with culture medium, myoblasts, or CD34+/CD90(-) cells. After 1 month, left ventricular ejection fraction was significantly higher in the CD34+/CD90(-) group than in the control and myoblast-injected hearts, which was associated with smaller fibrosis and greater angiogenesis. The low engraftment rate suggested a paracrine mechanism supported by the greater release of growth factors by CD34+/CD90(-) cells than by unsorted myoblasts. In conclusion, the human skeletal muscle does not harbor cardiac-specified cells but contains a CD34+ fraction endowed with an angiogenic potential providing superior functional and structural benefits.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.