Cell expansion control

Tomos, A.D. (1985). The physical limitations of leaf cell expansion. In Control of Leaf Growth, ed. N.R. Baker, W.J. Davies and C. Ong, pp. 1-33. Cambridge Cambridge University Press. 

Loss of E2F regulation by pRb impairs cell cycle control, and unregulated proliferation (clonal expansion) may lead to a tumor derived from that cell. 

Three different approaches for the cultivation of isolated hematopoietic cells have been described, the static, the stirred and the immobilized culture. Static cultivation takes place in very simple culture systems like well plates, tissue-culture flasks or gas-permeable culture bags [62, 63]. As the first two systems do not allow cell cultivation on a clinical scale, the latter is actually the most often used technique for stem cell expansion. All these systems have the advantage of being easy to handle, single-use devices, which enable an uncomplicated cell harvest. But all of them do not offer possibilities for process control or continuous feeding. This causes variations in culture conditions during fermentation (e.g., oxygen tension, pH, substrate, metabolite and cytokine concentrations). 

Cell expansion is mainly performed according to labor-intensive time-consuming protocols using open systems that increase the risks of microbiological or particulate contamination and supplementation with potent antibiotics to control these prob-... 

Currently, several strategies for progenitor cell expansion already exist. However, the most advanced protocols for hematopoietic cell expansion still show limited success. Tests with small volumes may work with conventional culture systems for proliferating blood cells such as lymphocytes, in T-flasks under a carbon dioxide (C02)-rich atmosphere, while higher volumes are generally used in controlled bioreactors (Noll et at, 2002 Cabrita et al., 2003). In these systems, fine control is necessary for all the physicochemical factors, such as pH, temperature, trace elements, cytokines (Noll et at, 2002). Each cell type requires specific conditions. 

As shown by measurement of root and hypocotyl elongation, the treatment with the RO fraction did not prevent the initial absorption of water by the seed, which is essentially a passive process. However, it effectively inhibited the ensuing expansion of these organs, which results from a combination of cell expansion and cell division. As late as 46 h after seed imbibition, no sign of cell division was visible in roots from seeds treated with 1 8- and 1 10-diluted RO fraction, and only occasional divisions, mainly in the procambial area, were observed after treatment at 1 14 dilution. By contrast, control roots resumed active cell division within 16 h after imbibition. As a conspicuous consequence of the inhibition of cell expansion/division activity, the apex of roots from treated seeds appeared distinctly... 

Light microscopy of radish radicles from a control seed after 16 h imbibition (a, c) and from a seed treated with 1 14-diluted reverse osmosis fraction, 46 h after imbibition. The root from the treated seed (b) is much shorter and coarser than the control (a). Cell expansion is strongly inhibited in the treated root (d) relative to the control (c). 

Granzyme B will cleave proteins at aspartate residues and will therefore activate pro-caspase 10 and can cleave factors like ICAD (inhibitor of caspase-activated DNase). However, Granzyme B can also directly activate caspase 3. In this way, the upstream signaling pathways are bypassed and there is direct induction of the execution phase of apoptosis. Recent findings indicate that this method of granzyme B cytotoxicity is critical as a control mechanism for T-cell expansion of type 2 helper T (Th2) cells. Moreover, findings indicate that neither death receptors nor caspases... 

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