The SAGE Encyclopedia of Stem Cell Research. Группа авторов
lacks a homogeneous environment because of the oxygen gradient and nutrients.
Ideally, bioreactors would offer high production capacity and high quality. Using sensors or probes, researchers can control and maintain hydrodynamic and physiological factors that affect proliferation and differentiation, including regulation of pH, nutrients, dissolved oxygen, extracellular matrix, and shear force. Perfusion and agitation reactors can improve control of oxygen supply and transfer of mass. Perfusion also reduces accumulation of toxic waste such as ammonia or carbon dioxide and, because it allows long-term high-density culture growth, reduces material costs, labor, and risk of contamination.
Stirred tank bioreactors have been studied for stem cell expansion and differentiation over the past several years because they are simple, scalable, dependable large-scale mammalian cell cultures. Stirring provides a homogenous environment for better cell growth and better mass transfer. On the negative, stirring might change the binding of the receptor and ligand, altering physiology and metabolism. Stir tank bioreactors allow easy monitoring of oxygen and pH. Stirred tank reactors have been used for adult stem cells, with a nine-fold higher expansion compared to static cultures. Stirred tank reactors have also had success with mouse cells.
The wave bioreactor uses disposable plastic bags inflated through ports that also allow air circulation. Rocking the bag in a wavelike motion allows good mixing and mass transfer and enhances oxygen transfer while holding the cells in suspension with low shear damage and bubble formation. Using sensors and feedback systems allow bioreactors to control oxygen tension more precisely. The system is safe in clinical environments and has been used in an industrial setting for stem cells and other mammalian cells, although the system is too expensive for most stem cell applications.
Transitioning to bioreactors may pose challenges. In the past few years, EMD Millipore has abandoned the Petri dish for significantly larger-scale bioreactors in anticipation of rapid future growth in the demand for stem cells. Already, stem cell therapy is utilized in the treatment of leukemia. One constraint is the availability of vast quantities of stem cells of suitable quality. In 2010, EMD Millipore began its stem cell initiative and provides reactors that comply with all the regulatory standards government demands. The EMD Millipore production system involves 3- to 50-liter bioreactors. Volume production comes with its own complications, including parameters different from those of the small-scale Petri dish production. New parameters include, but are not limited to, cell count in the initial culture, type of media to be used, temperature, air flow, and stir rate. The ability to differentiate and characteristic cell surface markers are often used to measure quality of a stem cell, but specific attributes of what makes a stem cell “good” and available to function from the beginning to the end of the process is lacking. Continuous monitoring of the bioreactor is necessary in order to check that the cells are retaining their ability to differentiate. One advantage of the bioreactor over the Petri dish is regular sampling is an option. This quality control allows immediate remediation if a flaw develops.
The bioreactor environment is somewhat delicate as well. Cells grow on tiny spheres that allow more surfaces for them to multiply on. However, the spheres make manipulation more of a challenge. In addition, there is no possibility of using an aggressive removal method since that process would destroy the cells and potentially damage the internal configuration of the bioreactor.
A major manufacturer of bioreactors is the Swiss firm Bioengineering. For 40 years, it has been producing commercial and customized, large and small bioreactors and fermentors. Its inventory reflects the variety available for potential buyers of bioreactors. Bioengineering offers a model designated RALF, a bench-top bioreactor in 2-, 3.7-, 5-, and 6.7-liter sizes. It comes in basic and advanced models, takes little space and power, and has the capability of doing cell and microbial culture because of the free configuration of gas lines. It also has process management software that includes process automation, recipe features, management of access, and an audit trail. The turn key system is available from stock in two weeks or less. Other models are larger and more sophisticated, including the P, which comes in sizes ranging from 100 to 1,000 liters. It is a production-scale bioreactor and is marketed as highly flexible, with open frame construction for ease of maintenance and installation and with a modular control system that promotes fast process change. It is also customizable and reprogrammable.
Celltrion Inc. in Korea has the largest cell cultivation plant in the world, a 300,000-liter facility that includes four production trains with five 16,000-liter bioreactors each, six other production trains with five 19,000-liter bioreactors, and 100-plus tanks for buffering, harvesting, and other functions. With storage and quality control facilities, the site positions the company founded in 2002 to become a major producer of cells.
Bioreactors can be small enough to fit on a desk or large enough to require a tank farm. They have many types of configurations. They can be expensive, and growing stem cells at the appropriate scale and quality can be a challenge. However, they represent a niche that cannot be filled by the Petri dish.
John H. Barnhill
Independent Scholar
See Also: Stem Cell Aging; Stem Cell Companies: Overview; Tissue Engineering (Scaffold).
Further Readings
BiOENGiNEERiNG. “Bioreactors, Fermentors and BiO●CoMPONENTS™.” http://www.bioengineering-inc.com/bioreactors_fermentors/bf_p.html (Accessed May 2014).
____________. “Celltrion, Inc.” http://www.bioengineering-inc.com/celltrion_inc.html (Accessed May 2014).
Emdgroup. “Stem Cells From Bioreactors.” Emdgroup Magazine (August 14, 2013). http://magazine.emdgroup.com/en/Life_and_Assistance/stem_cell_initiative/Stem_cells_from_bioreactors1.html?magazineRateArticle=tcm:2292–114374–64
Liu, Meimei, Ning Liu, Ru Zang, et al. “Engineering Stem Cell Niches in Bioreactors.” World Journal of Stem Cells, v.5/4 (October 26, 2013). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812517/
Liu, N., R. Zang, S.-T. Yang, et al. “Stem Cell Engineering in Bioreactors for Large-Scale Bioprocessing.” Engineering in the Life Sciences, v.14 (2014). http://onlinelibrary.wiley.com/doi/10.1002/elsc.201300013/full
Bladder: Cell Types Composing the Tissue
Bladder: Cell Types Composing the Tissue
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Bladder: Cell Types Composing the Tissue
Human tissues are subject to permanent damage and injuries, and stem cells can help to regenerate these tissues. Understanding stem cells and their differentiation and regeneration process will help understand how they can be used in repair of bladder dysfunctions. To have an in-depth understanding of the use of stem cells in bladder tissue regeneration and therapy, it is also essential to understand the anatomy of the bladder.
Urinary Bladder
The hollow muscular organ in the pelvic area is known as the urinary bladder. It is spherical in shape and is approximately the size of a large grapefruit. The function of the urinary bladder is to collect and store the urine. The urinary bladder is connected to the kidneys by means of small tubular structures known as ureters. The base of the bladder is connected to the urethra, which helps in draining the urine.
Bladder Anatomy
The sphincter