A Primary Culture System of Human Colon Carcinoma Cells and its Use in Evaluating Differentiation Therapy
Leonard H. Augenlicht in Cell and Molecular Biology of Colon Cancer, 2019
An efficacious differentiation protocol has been to induce terminal differentiation, as defined by a loss of infinite proliferative capacity, in the vast majority of cells. Cell culture systems have been developed to dissect differentiation pathways of hematopoietic lineages and have demonstrated terminal differentiation of stem cells to end-stage, nondividing cells such as macrophages, megakaryocytes, and erythrocytes.10 Terminal differentiation of hematopoietic tumor cells has been demonstrated using similar clonal cell culture systems. DMSO induced Friend erythroleukemia cells to terminally differentiate, with a discrete probability per cell cycle, from a cell stage with unlimited growth potential first to partially differentiated, hemoglobin-containing cells with a potential for only four or five cell divisions and finally to endstage, nondividing cells. The progeny of each tumor cell which was induced to differentiate was analyzed in a clonal plasma clot assay system.11
Mechanism of Action of Alitretinoin
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
Alitretinoin is a pan-retinoic acid agonist. It has the ability to bind and activate all subclasses of intracellular retinoid RAR and RXR receptors (RAR-α, RAR-β, RAR-γ, RXR-α, RXR-β, and RXR-γ). These receptors act as transcription factors to regulate the expression of genes that control cellular differentiation and proliferation. Several pharmacodynamic processes take place, and the expressed proteins cause the clinical and therapeutic effects of alitretinoin (4). The mechanism of action of alitretinoin can be considered under two main subheadings (1,4):Antiproliferative-apoptotic effectImmunomodulatory-anti-inflammatory effect
Factors Influencing Growth and Differentiation of Normal and Transformed Human Mammary Epithelial Cells in Culture
George E. Milo, Bruce C. Casto, Charles F. Shuler in Transformation of Human Epithelial Cells: Molecular and Oncogenetic Mechanisms, 2017
Maturation, or terminal differentiation, may also follow a biological pathway distinct from cellular senescence observed in vitro. Normal human fibroblasts and epithelial cells in culture display a limited, fixed number of population doublings which varies with cell type and culture conditions. For example, normal HMEC grown in the serum-free medium MCDB 170 will undergo 45 to 80 population doublings, depending upon the individual specimen donor, and then show no net increase in cell number. These nondividing cells may maintain viability for months in culture. It is likely that the controls which limit the number of times a given cell may complete the cell cycle are distinct from those which lead to a mature, nondividing, and ultimately nonviable phenotype. Thus, a cell may senesce in culture without ever exhibiting the phenotype of the most mature or functionally differentiated cell type in its lineage.
Biology of Cancer; From Cellular Cancerogenesis to Supracellular Evolution of Malignant Phenotype
Published in Cancer Investigation, 2018
Phenotype represents the morphological and functional expression of the body/cell, and depends by three distinct factors: inherited genotype, inherited epigenetic factors, and non-inherited environmental factors. During cellular differentiation, developmental options are progressively restricted in order to favor evolution towards a specific morphology and function, terminal differentiation being consequently limited and possible only along this lineage. Evolution of cells in different directions (towards neuron, nephron, etc.) would be channeled through intervention of distinct epigenetic and environmental factors. As a consequence, the cell differentiation and phenotype expression of mature cells depend in great extent by extracellular factors, being different for different cells even if all these cells incorporate identical genomic data (14).
Study of mutation from DNA to biological evolution
Published in International Journal of Radiation Biology, 2019
Masako Bando, Tetsuhiro Kinugawa, Yuichiro Manabe, Miwako Masugi, Hiroo Nakajima, Kazuyo Suzuki, Yuichi Tsunoyama, Takahiro Wada, Hiroshi Toki
Second, biological objects live in the world, where a lot of different possibilities are available. For example, the fate of a stem cell is determined by its ability to respond various epigenetic environmental conditions against mutational or environmental stimulus. In order to describe such process with time irreversibility, the Waddington’s landscape (Waddington 1957) is usually used. It indicates that the fates of stem cells are progressively determined to become various kinds of somatic cells during the cellular differentiation process. On the other hand, physicists had thought that the time development is uniquely determined from our basic equation of motion, where a particle follows its unique path once its initial condition is fixed, namely the rule of nature satisfies the time reversal symmetry, until they found that the irreversible processes commonly exist even in physical phenomena as seen in the phase transition. Now we can find very much similar pictures of landscape in the string cosmology to describe the creation of universe in astrophysics to display the pre-Big Bang universe. Interestingly, the origin of two landscape pictures are traced back to the ‘catastrophe theory’ proposed by Thom, who took contact with Waddington in the early 1940s.
Regenerating β cells of the pancreas – potential developments in diabetes treatment
Published in Expert Opinion on Biological Therapy, 2018
A major obstacle in translating the discoveries into clinical use, however, is safety concern: the high proliferative nature of stem cells, if not reined in by terminal differentiation, can lead to tumor formation in vivo. Indeed, transplantation of hESC-derived pancreatic endocrine precursor cells into mice has resulted in the formation of teratomas in 2.2% of recipient mice [85]. One strategy to mitigate the problem is to place the transplanted cells in an encapsulation device – this will not only allow the transplanted cells to be removed should they grow into tumors, but also protect them from immune attack. In the past few years, key progresses are made in the development of encapsulation devices that allow hESC-derived precursor cells to differentiate and function in vivo [90–93]. Most notably, the microencapsulation device, TheraCyte, featuring a bilaminar polytetrafluoreoethylene membrane system, has shown full capacity to allow the maturation and function of hESC-derived pancreatic progenitors inside the device following transplant into mice, resulting in the reversal of diabetes within 3 months [90,91,93]. Vegas et al. has encapsulated SC-β cells with alginate derivative-based polymers and has successfully implanted them into immune-competent mice without immunosuppression, achieving long-term glycemic control in diabetic mice [92].