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Single-Cell Analysis in Cancer
Published in Inna Kuperstein, Emmanuel Barillot, Computational Systems Biology Approaches in Cancer Research, 2019
Inna Kuperstein, Emmanuel Barillot
Multicellular organisms consist of different cell types that give rise to a multitude of organs and tissues with distinct functions. These cell type-specific functions are acquired during development in a process called cellular differentiation, whereby pluripotent stem cells undergo a sequence of gene expression changes to give rise to all mature cell types. Moreover, in adult organisms tissue-resident stem cells remain crucial for tissue homeostasis in organs with high turnover such as skin, gut or blood, where mature cell types constantly need to be replenished within a few days to maintain organ function.3 Yet in other organs, such as the liver, stem cells show lower turnover at homeostatic conditions, but can boost their proliferation significantly to regenerate tissue after injury.4
Epigenetic control of cell fate and behavior
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Recently, small RNAs have been described to play large roles in mediating states of cellular differentiation through modulating gene expression states, generally through silencing mechanisms. Small double-stranded RNA molecules, called pre-microRNAs (pre-miRNA), are produced from target genes and processed by the RNA-induced silencing complex (RISC) containing the Dicer protein (Krol et al. 2004). Dicer cleaves the double-stranded structure into two single strands, one of which is the complement of the target gene transcript. The single-stranded mature miRNA then associates with a member of the Argonaute family of proteins, which facilitates base pairing between the miRNA and the target messenger RNA (mRNA). The formation of the new double-stranded structure results in the degradation of the target mRNA, which can no longer be translated to produce a functional protein (Valencia-Sanzhez et al. 2006). The complement of miRNAs within a cell differs based on cell identity and appears to be important in directing the proper development of tissues within an organism (Sayed and Abdellatif 2011). Taken together, the myriad of epigenetic control mechanisms can largely influence states of cellular differentiation, a process that we must hope to control within the context of directed regeneration of complex structures.
Medium Design for Cell Culture Processing
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
Many cell lines and primary cells explanted from tissues will not proliferate if provided with basal medium alone, as basal medium does not contain growth factors or other factors necessary for growth. Growth supplements that may be added to basal medium include growth factors, phospholipids, soy hydrolysate, and serum. These supplements may promote cell growth by providing molecules that modulate specific signaling pathways, or by filling some nutritional needs (such as delivering cholesterol). Some signaling molecules, instead of stimulating cell growth, trigger a signaling pathway that directs cellular differentiation or maintains cells at a particular differentiation state.
Immobilized RGD concentration and proteolytic degradation synergistically enhance vascular sprouting within hydrogel scaffolds of varying modulus
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Yusheng J. He, Martin F. Santana, Madison Moucka, Jack Quirk, Asma Shuaibi, Marja B. Pimentel, Sophie Grossman, Mudassir M. Rashid, Ali Cinar, John G. Georgiadis, Marcella K. Vaicik, Keigo Kawaji, David C. Venerus, Georgia Papavasiliou
In this study we utilized a statistical DOE methodology and full factorial experimental analysis to determine the individual and combined effects of matrix stiffness, proteolytic degradation and immobilized RGD cell adhesion ligand concentration on vascular sprouting in 3 D culture using PEG-based hydrogels as a tunable biomaterial platform. The main advantage of application of the DOE analysis in the present study is that it enabled screening of the interactions of multiple matrix cues which would otherwise only reveal effects of individual as opposed to factor interactions. The majority of studies in engineering biomaterials for vascularized tissue formation have investigated the effect of one or two matrix cues at a time without considering potential interactions of the investigated factors on vascular responses [7,9–11,19–22]. In this study, application of modular synthetic scaffolds in combination with DOE allowed us to identify the strong synergistic impact of immobilized RGD concentration and proteolytic scaffold degradation rate leading to optimal vascular sprouting responses in 3 D culture over a range of matrix properties investigated (Table 1). To the best of our knowledge, this is the first time that statistical DOE has been used to study the interplay between modulus, proteolytic degradation and adhesion ligand concentration on neovascularization. These matrix cues form the fundamental basis for engineering functional tissue replacements that require a specific stiffness, composition of integrin-binding peptide ligands and degradation rates to promote cellular differentiation and vascularized matrix remodeling.
Dexamethasone- loaded polymeric porous sponge as a direct pulp capping agent
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Amjad Alagha, Abdulwahab Nourallah, Sahar Alhariri
Collagen type-I is the basic protein in animals and it is particularly widespread in the skin, tendons, bones, and dentin, where its function is to absorb and transfer forces [28]. Because of the special properties of collagen that promote the adhesion, proliferation and cellular differentiation, it has been extensively studied in the design of tissue engineering scaffolds; since porous collagen scaffolds have distinctive physical, chemical and biological properties for using in tissue engineering [29,30]. One study found the formation of a dentin bridge in 73% of teeth of monkeys after capping its exposed pulp with an enriched collagen solution [31].
Influence of pore sizes in 3D-scaffolds on mechanical properties of scaffolds and survival, distribution, and proliferation of human chondrocytes
Published in Mechanics of Advanced Materials and Structures, 2022
Zahra Abpeikar, Peiman Brouki Milan, Lida Moradi, Maryam Anjomshoa, Shiva Asadpour
Tissue engineering is using cells and three-dimensional scaffolds to obtain better tissue repair and regeneration outcomes. The scaffolds can provide an excellent environment for cell adhesion, proliferation, migration, and differentiation in the injured tissue [35]. Results of the swelling test showed that pore sizes of the scaffold affected water absorption behavior. As mentioned before, scaffold permeability plays an essential role in the nutrient and waste transport within it. The only way to transfer nutrients to cells inside the scaffold and excretion of waste metabolites is through permeability and water uptake. Also, in the early stages of in vivo studies, before angiogenesis, permeability is a very important process [36–38]. Naturally, permeability for cartilage tissue is essential due to the joint lubrication, nutrient transport and fluid mechanics [37, 38]. Also, since meniscus tissue has few blood vessels, it is mostly nourished by synovial fluid diffusion and this tissue behaves like a sponge by absorption of synovial fluid [39–41]. Previous researches demonstrated that the permeability of cartilage related to the variety of factors including composition, the structure depth and the mechanical load applied to it [37, 42]. Permeability of cartilage tissue reduces with enhancing tissue depth because of augmented proteoglycans amount and to a lesser extent, collagen fibers. Periodic alterations in biophysical stimuli that occur because of fluid circulation within the cartilage tissue during mechanical loading are affected by the construct and permeability of the tissue. Remarkably, the extent of compression and fluid shear stresses in the scaffold or tissue, have been recognized as potential stimuli for cellular differentiation or functional adaptation, and both are influenced by permeability [43–45]. Scaffold permeability also affects the degradation rate of biodegradable scaffolds [46, 47].