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Stem Cell Engineering
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Yi Sun Choi, Kisuk Yang, Jin Kim, Seung-Woo Cho
Besides stem cell migration, the signal gradient generated in microfluidic systems can exert significant effects on stem cell differentiation. In the early development of the vertebrate nervous system, the gradient of diffusible paracrine factors plays important roles in stem cell differentiation and various functional developments. Cells recognize their position through the gradient of extracellular signaling molecules and determine their developmental fate. Signaling molecules like sonic hedgehog (Shh), fibroblast growth factor (FGF), and bone morphogenic protein (BMP) engage in an interplay to guide stem cell differentiation along the dorsoventral and anteroposterior axes (Figure 4.7; Park et al. 2009). Inductive signaling molecules regulate the development of the neural plate at the mid-hindbrain junction (FGF8) and floor plate (Shh). The cross-sectional image in Figure 4.7 illustrates the Shh and BMP gradients, which specify ventral neurons and dorsal neurons, respectively. By replenishing reagents in the microfluidic chip using an osmotic pump, different factors in two fluid streams can generate multiplex gradient via diffusion (Park et al. 2009). Thus, the concentration gradient of Shh, BMP, and FGF that is similar to that of dorsoventral and anteroposterior axes during the early development of the vertebrate nervous system can be formed on the gradient-generating microfluidic chip. Such a chip with multiplex factor gradients had been used with hESC-derived NPCs to stimulate an increased proliferation rate and the expression of Tuj in the region with a combination of Shh and FGF8 (Park et al. 2009). This phenomenon proves the efficacy of the multigradient chip, since the individual treatment of each factor had minimal influence on the hESC-derived NPCs.
Fundamentals of biology and thermodynamics
Published in Mohammad E. Khosroshahi, Applications of Biophotonics and Nanobiomaterials in Biomedical Engineering, 2017
This is part of a complex system of cellular communication that governs basic activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue haemeostasis. There are three types of signalings: (a) Endocrine corresponds to hormonal signaling of distant cells, (b) Paracrine is signaling from one cell to an adjacent cell, and (c) Autocrine, which is the same cell simulation signal.
Tissue Engineering: overview of biochemical data and mechanical modeling
Published in Benjamin Loret, Fernando M. F. Simões, Biomechanical Aspects of Soft Tissues, 2017
Benjamin Loret, Fernando M. F. Simões
Hormones are produced by specialized cells, gathered in glands. Hypothalamus, hypophysis, thyroid, ovary, testis are endocrine glands. Depending whether they are in the cells they are created, in the neighborhood of these cells, or at distance after being transported by blood, hormones are termed autocrine, paracrine and endocrine, respectively. Sometimes, paracrine regulators, which diffuse in the extracellular fluid to the target cell are termed local mediators to contrast with endocrine hormone regulation.
Influence of extracellular cues of hydrogel biomaterials on stem cell fate
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Haley Barnett, Mariya Shevchuk, Nicholas A. Peppas, Mary Caldorera-Moore
Hydrogel properties can be tuned to regulate stem cell behavior through both cell-matrix and cell-cell interactions. Hydrogel properties such as stiffness and viscoelasticity will affect cell-matrix interactions through the process of mechanotransduction, where cells transduce a physical stimuli into biochemical signals. There have been numerous studies demonstrating that the stiffness and viscoelastic properties of a hydrogel can alter a cell’s attachment rates [36], cell spreading [44], proliferation efficiency [45,46], and differentiation potential [28]. Hydrogel stiffness is typically controlled through crosslinking density by varying the concentration of polymer or crosslinking molecule and has been varied to achieve elastic moduli of tissues ranging from brain (0.1–1 kPa) to bone (∼100 kPa) [28]. Other tunable properties of hydrogels, such as porosity and degradation, have been demonstrated to influence cell-cell interactions [47,48]. Cell-cell interactions, whether they occur through direct cell surface receptor interactions or paracrine signaling, aid in controlling cell function [49]. Therefore, it is important to consider these properties when designing a hydrogel scaffold as changes in cell-matrix and cell-cell interactions will influence a cell’s decision to attach, proliferate or differentiate. This highlights the importance of material selection when designing a hydrogel for tissue engineering applications, as different polymers can impart different biological, mechanical, and degradative properties to the hydrogel. A brief overview of polymers used for hydrogels are discussed below.
Lead alters intracellular protein signaling and suppresses pro-inflammatory activation in TLR4 and IFNR-stimulated murine RAW 264.7 cells, in vitro
Published in Journal of Toxicology and Environmental Health, Part A, 2019
R.J. Williams, E. Karpuzoglu, H. Connell, D.J. Hurley, S.D Holladay, R.M. Gogal
Macrophage-derived NO possesses many important roles in host immunity. Suppression of NO by Pb as seen in this study might result in numerous negative outcomes, in vivo. One obvious outcome would be impaired macrophage NO destruction of encountered pathogens, increasing an organism’s susceptibility to infection (Aktan 2004; Dorpinghaus et al. 2016; MacMicking, Xie, and Nathan 1997). However, the downstream consequences of reduced NO production may have a greater impact on the immune system. The macrophage links innate and adaptive immune systems through antigen presentation and cell surface protein interaction with T helper (Th) cells. Another important role of NO in the immune system is as a paracrine signaling molecule that was found to suppress proliferation of Th cells stimulated by the Th cell mitogen Concanavalin A (Con A) (Albina, Abate, and Henry 1991; Bingisser et al. 1998; Sato et al. 2007). Therefore, NO is a key regulatory molecule involved in Th cell proliferation during macrophage/Th cell interaction. Previous investigators demonstrated that Pb induced T cell production of IL-4, while inhibiting production of IFN-γ promoting the proliferation of Th2 cells (Heo, Parsons, and Lawrence 1996; Miller et al. 1998). Based upon these observations, it is plausible that a Pb-exposed individual, when challenged by a pathogen, may exhibit a shift toward increased IL-4 production driving naïve Th cells towards Th2 cells encountering activated macrophages with depressed NO secretion.
Constructing artificial urinary conduits: current capabilities and future potential
Published in Expert Review of Medical Devices, 2019
Jan Adamowicz, Shane V. Van Breda, Tomasz Kloskowski, Kajetan Juszczak, Marta Pokrywczynska, Tomasz Drewa
In contrast, most of the experimental research on urinary tract reconstruction uncritically indicated better regeneration outcomes in cell-seeded grafts [23–25]. Mesenchymal stem cells, for instance, stimulate smooth muscle regeneration within the urinary tract wall via the Hedgehog pathway. Nevertheless, this supporting paracrine signaling seems to decrease rapidly after implantation due to poor stem cell survival and is thus overwhelmed by pro-fibrotic factors [26]. Shortly after, a similar study using a rabbit model was published by Liao et al. In this setting, urothelial cells were seeded on the inner layer of a tubular shaped BAM. After eight weeks, a stratified urothelium with an abundant vascular network located under a reconstituted basement membrane had formed. Cardinal urothelial markers such as AE1/AE3, uroplakin Ⅲa, and ZO-1 confirmed the development of a mature phenotype.