Tissue-engineered 3D cancer-in-bone modeling: silk and PUR protocols
Ushashi C. DadwalCarolyne FalankHeather FairfieldSarah LinehanClifford J. RosenDavid L. KaplanJulie A. SterlingMichaela R. Reagan
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Multicellular organism
Cells in obligately multicellular organisms by definition have aligned fitness interests, minimum conflict, and cannot reproduce independently. However, some cells eat other cells within the same body, sometimes called cell cannibalism. Such cell-in-cell events have not been thoroughly discussed in the framework of major transitions to multicellularity. We performed a systematic review of 508 articles to search for cell-in-cell events across the tree of life, the age of cell-in-cell-related genes, and whether cell-in-cell events are associated with normal multicellular development or cancer. Out of the 38 cell-in-cell-related genes found in the literature, 14 genes were over 2.2 billion years old, i.e., older than the common ancestor of some facultatively multicellular taxa. Therefore, we propose that cell-in-cell events originated before the origins of obligate multicellularity. Cell-in-cell events are found almost everywhere: across some unicellular and many multicellular organisms, mostly in malignant rather than benign tissue, and in non-neoplastic cells. Thus, our results show that cell-in-cell events exist in obligate multicellular organisms, but are not a defining feature of them. The idea of eradicating cell-in-cell events from obligate multicellular organisms as a way of treating cancer, without considering that cell-in-cell events are also part of normal development, should be abandoned.
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Filamentous organisms represent an example where incomplete separation after cell division underlies the development of multicellular formations. With a view to understanding the evolution of more complex multicellular structures, we explore the transition of multicellular growth from one to two dimensions. We develop a computational model to simulate multicellular development in populations where cells exhibit density-dependent division and death rates. In both the one- and two-dimensional contexts, multicellular formations go through a developmental cycle of growth and subsequent decay. However, the model shows that a transition to a higher dimension increases the size of multicellular formations and facilitates the maintenance of large cell clusters for significantly longer periods of time. We further show that the turnover rate for cell division and death scales with the number of iterations required to reach the stationary multicellular size at equilibrium. Although size and life cycles of multicellular organisms are affected by other environmental and genetic factors, the model presented here evaluates the extent to which the transition of multicellular growth from one to two dimensions contributes to the maintenance of multicellular structures during development.
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The diversity of multicellular organisms is, in large part, due to the fact that multicellularity has independently evolved many times. Nonetheless, multicellular organisms all share a universal biophysical trait: cells are attached to each other. All mechanisms of cellular attachment belong to one of two broad classes; intercellular bonds are either reformable or they are not. Both classes of multicellular assembly are common in nature, having independently evolved dozens of times. In this review, we detail these varied mechanisms as they exist in multicellular organisms. We also discuss the evolutionary implications of different intercellular attachment mechanisms on nascent multicellular organisms. The type of intercellular bond present during early steps in the transition to multicellularity constrains future evolutionary and biophysical dynamics for the lineage, affecting the origin of multicellular life cycles, cell–cell communication, cellular differentiation, and multicellular morphogenesis. The types of intercellular bonds used by multicellular organisms may thus result in some of the most impactful historical constraints on the evolution of multicellularity.
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Every type of cell has its own special features that differentiate its members qualitatively from cells of other types. Within the same type of cells, however, every single cell also has its own unique characteristics that deviate itself from other individual cells, although they are alike collectively. These kinds of individual differences between cells are described here as cell individuality, which says basically that, within a cell population or even within a multicellular organism, every cell is a unique individual living being; and no single cell could be completely identical to another, regardless of how similar to each other they are. The individuality of a single cell can be represented by all sorts of cell characteristics, which are countless and range from physiological activities to molecular constituents. These individual differences in cell characteristics are generally presented much more in degree or in quantity, rather than in kind or in quality. Moreover, such cell individuality or quantitative variations within or even between cell populations may also play a basic role in the pathogenesis of disease, and particularly in the susceptibility of cells to the disease process.
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What makes a cell? ‘The nature of cells’ considers the cell ℄ the smallest unit of life ℄ by looking at basic cell characteristics, membranes and cell walls, and the interior of the cell. The distinction between prokaryotic and eukaryotic cells is explained. The main characteristic of eukaryotic cells is their ability to alter their shape, components, and metabolism to fulfil a particular task — to differentiate — a facility which allows them to come together and form multicellular tissues, to combine those tissues into organs, and then form an entire organism such as a human being. Finally, in vitro studies, where plant or animal cells are grown in laboratories, are discussed.
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Benefits of increased size and functional specialization of cells have repeatedly promoted the evolution of multicellular organisms from unicellular ancestors. Many requirements for multicellular organization (cell adhesion, cell-cell communication and coordination, programmed cell death) likely evolved in ancestral unicellular organisms. However, the evolution of multicellular organisms from unicellular ancestors may be opposed by genetic conflicts that arise when mutant cell lineages promote their own increase at the expense of the integrity of the multicellular organism. Numerous defenses limit such genetic conflicts, perhaps the most important being development from a unicell, which minimizes conflicts from selection among cell lineages, and redistributes genetic variation arising within multicellular individuals between individuals. With a unicellular bottleneck, defecting cell lineages rarely succeed beyond the life span of the multicellular individual. When multicellularity arises through aggregation of scattered cells or when multicellular organisms fuse to form genetic chimeras, there are more opportunities for propagation of defector cell lineages. Intraorganismal competition may partly explain why multicellular organisms that develop by aggregation generally exhibit less differentiation than organisms that develop clonally.
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▪ Abstract Multicellular organisms appear to have arisen from unicells numerous times. Multicellular cyanobacteria arose early in the history of life on Earth. Multicellular forms have since arisen independently in each of the kingdoms and several times in some phyla. If the step from unicellular to multicellular life was taken early and frequently, the selective advantage of multicellularity may be large. By comparing the properties of a multicellular organism with those of its putative unicellular ancestor, it may be possible to identify the selective force(s). The independent instances of multicellularity reviewed indicate that advantages in feeding and in dispersion are common. The capacity for signaling between cells accompanies the evolution of multicellularity with cell differentiation.
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Cancer is a disease of multicellular organisms in which, following the manifestation of genetic alterations, one neoplastic cell develops into a tumour mass which grows escaping all the normal rules of cell coexistence which regulates multicellular organisms. We define as malignant tumour one which spreads throughout the body forming metastases, and as benign tumour one which is localized and non-invasive. Cancer is found mostly throughout the Metazoa (i.e. multicellular animals) but is also present in some plants. A simpler neoplastic-like behaviour, so-called cheating, is present instead even in the simplest multicellular bacterial organisms, where cells can start to grow excessively, escaping normal behaviour.
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