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Cancer Biology and Genetics for Non-Biologists
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
Your cells have to communicate, and they do not all live in isolation. Cells send and receive messages via signalling molecules. The signals can tell a cell to grow, produce particular proteins, produce a metabolic response or to die (apoptosis). The signals sent and received are usually called ligands and can be molecules, proteins or ions. Signals can be received from other nearby cells or from afar, the four types being, Paracrine signalling: Signalling by nearby cells allowing similar cells to act similarly• Synaptic signalling: Signalling by electrical impulses through nerve cellsAutocrine signalling: Signalling of a cell to itselfEndocrine signalling: Signalling from distant endocrine cells, e.g. the pancreas
Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
There are three forms of signalling mediated by secreted molecules: paracrine, synaptic, and endocrine. Signalling molecules secreted by cells to act as local mediators, which only effect cells in the immediate environment, must not be allowed to diffuse too far, so are rapidly taken up by the neighbouring cells, or destroyed by extracellular enzymes, or immobilised by the extracellular matrix. This is called paracrine signalling. For multicellular organisms to be able to coordinate cell behaviour across the entire organism, some signalling molecules must travel far afield to distant cells. This is achieved in two ways: by networks of nerve cells and by the action of hormones. Synaptic signalling involves routes of neurones along which electrochemical impulses travel to stimulate the release of chemical signals called neurotransmitter, which carry the signal on between neurones across gaps called synaptic junctions and propagate the electrochemical impulse in the adjoining neurone. Endocrine cells release hormones, which are signalling molecules that travel in the bloodstream of an animal (or sap in plants) and thus distribute widely throughout the body, enabling signals to be carried to distant cells. Since this process relies on diffusion, it is much slower than synaptic signalling.
Actions of Dopamine on the Skin and the Skeleton
Published in Nira Ben-Jonathan, Dopamine, 2020
The same investigators [21] also used diabetic rats with defective skin healing properties (Figure 11.5). Application of conditioned media harvested from the Ad-MSCs cultured on Dopa-BC, accelerated wound closure in the diabetic rats, enhanced vascularization, and promoted macrophage switching from a proinflammatory M1 to a pro-healing and anti-inflammatory M2 phenotype in the wound bed. The authors concluded that coating with PDA represents an effective method for enhancing the beneficial paracrine function of MSCs. These findings offer a novel strategy for accelerating tissue regeneration by guiding the paracrine-signaling network.
Epicardial transplantation of autologous atrial appendage micrografts: evaluation of safety and feasibility in pigs after coronary artery occlusion
Published in Scandinavian Cardiovascular Journal, 2022
Annu Nummi, Tommi Pätilä, Severi Mulari, Milla Lampinen, Tuomo Nieminen, Mikko I. Mäyränpää, Antti Vento, Ari Harjula, Esko Kankuri
The number of cardiomyocytes in adult heart remains approximately the same during a lifetime [41,42] and the growth in adult mammalian heart occurs in cell size rather than increase in cells. Despite numerous efforts to generate new cardiac muscle cells via stem/progenitor cell technologies, there is no desired outcome. Bin Zhou and colleagues provided evidence that there is no cardiomyocyte producing stem cell population in the adult mammalian heart [43]. Yet there are promising results documented in improvement of LVEF, ventricular remodeling, and reduction of the infarct scar in both preclinical and clinical studies with stem cells [38–45]. With this paradoxical result, further investigations, especially focusing on elucidating the mechanism of action, on cell therapy in heart failure are necessary. The effect and importance of paracrine signaling, different delivery methods, cell sources, and used cell types all need better understanding and more large-scale, randomized trials.
Evaluation of canine bone marrow-derived mesenchymal stem cells for experimental full-thickness cutaneous wounds in a diabetic rat model
Published in Expert Opinion on Biological Therapy, 2021
Deepika Bist, A. M. Pawde, Prakash Kinjavdekar, Reena Mukherjee, K. P. Singh, Med Ram Verma, Khan Sharun, Amit Kumar, Pawan K. Dubey, Divya Mohan, Amit Verma, G. Taru Sharma
The usefulness of MSC in accelerating wound healing in veterinary practice has not been evaluated much despite increasing evidence that MSCs have the potential to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). MSCs therapeutically applied to the wound may release soluble factors that stimulate proliferation and migration of the predominant cell types in the wound [18]. Consequently, paracrine signaling has potential beneficial effects on angiogenesis, epithelialization, and fibroblast proliferation during wound repair. Nonetheless, several reports suggest that MSCs differentiate into epidermal keratinocytes, endothelial cells, and pericytes in vivo [34,35]. Furthermore, it has been reported that none of the xenogenic transplanted MSCs proliferated in an uncontrolled manner, and there was no sign of tumor formation in cutaneous tissue [18].
miRNA-based therapeutic potential of stem cell-derived extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury
Published in International Journal of Radiation Biology, 2019
Ron J. Leavitt, Charles L. Limoli, Janet E. Baulch
EVs were originally thought to be a ‘disposal mechanism’ for cellular garbage (Pan and Johnstone 1983), but have now been shown to be important both for cell-to-cell communication and microenvironment maintenance (Théry 2011). This autocrine/paracrine signaling mechanism is now considered a short or long distance mode of communication common to almost all cells and tissues of the body. The classification of various EVs is of some debate, however, it is generally accepted that these membrane-bound vesicles are divided into two groups based on size and mode of formation. Microvesicles (MVs) tend to be larger – ranging from 100 nm to 1 µm – and are created by direct assembly and outward budding from the cell membrane (Bucki et al. 1998). External stimuli such as hypoxia or the influx of Ca2+ can trigger the release of MVs from the cell (Bucki et al. 1998). The biogenesis of exosomes which tend to be smaller – 30 to 100 nm – involves the release of intraluminal vesicles contained inside the endosome-derived multivesicular body (MVB) by fusion with the plasma membrane (György et al. 2011). During this process, the bioactive cargo from the cytosol is sorted into the tiny vesicles. MVB formed by this mechanism release exosomes into the extracellular space when they fuse with and bud off from the plasma membrane (Cocucci and Meldolesi 2015). The release of exosomes is known to involve Rab GTPases (Abels and Breakefield 2016).