Stem Cells
Cell manufacturing scale-up at Paragon Bioservices
banks are provided either in frozen stocks or ‘ready- to-use’ high throughput motifs. Contract manufac- turing companies, such as Paragon Bioservices, are actively involved in addressing this need. Many companies have developed unique stem cell technologies and are now relying on service companies to produce and distribute these tool platforms to a wide range of users. Vivo Biosciences, Inc has developed a novel human bio- matrix system for cultivating human stem cells (eg derived from adipose, CNS and MSC) for long- term growth and differentiation studies in both 2D and 3D bioscaffold culture. This approach is in development for use in real-time cell-based assays for the xCELLigence System, co-developed by Roche-ACEA.
In 2006, scientists made more news in stem cell research when they identified conditions that would allow some specialised adult cells to essen- tially be reprogrammed genetically to assume a cell-like state, by being forced to express genes for maintaining the defining properties of embryonic stem cells. This type of stem cell is called induced pluripotent stem cells (iPSCs). Unlike embryonic stem cells, iPSCs are made in the lab (while adult stem cells naturally occur in the human body). Since they are obtained from the patient’s own cells (such as from skin) the ethical issues that plagued human embryonic stem cells are avoided. Patient-specific iPSCs can offer a supply of genetically identical cells that can be differentiated into all somatic cell types for potential use in regenerative therapies or drug screening and test-
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ing. As the techniques for generation of iPSC lines are constantly improving and include small mole- cule effectors, new uses for human iPSCs are emerging. These include in vitro disease modelling, high throughput drug discovery and population specific screening. This technology promises to rev- olutionise the field of medicine and offers new hope for understanding and treatment of numer- ous diseases. It is widely believed that iPS cells have the greatest potential for drug discovery and patient therapies. Testing the toxicity of pharmaceutical candi- dates in lab animals to support the safety for human clinical trials is notoriously unreliable. Often compounds that appear safe in rodents prove to be toxic in humans. In order to predict toxicity in cell models, many investigators are using embryonic and somatic progenitor cells to monitor the behaviour of stem cells exposed to new compounds via disruption of cell-to-cell inter- actions and interference with expected develop- ment or differentiation. Using embryonic stem cells or iPSCs to create human heart cells could be a viable and scientifically exciting alternative to ani- mal testing – saving precious time and money spent on the wrong drug candidates.
Pro-arrhythmia (development of cardiac arrhyth- mias as a pharmacological side-effect) has become the single most common cause of the withdrawal or restrictions of previously marketed drugs. The development of new medications, free from these side-effects, is hampered by the lack of an in vitro assay for human cardiac tissue. According to Caspi, et al (Stem Cells Dev 2009 18(1):161-72), human embryonic stem cell-derived cardiomyocytes (hESC-CMs) assessed with a combination of single cell electrophysiology and microelectrode array (MEA) mapping can serve as a novel model for electrophysiological drug screening.
Cellular Dynamics has the ability to generate iPSC lines from the blood samples of hypertensive patients. The iPSC lines can then be differentiated into ventricular heart cells for use in genetic stud- ies. Differentiated iPSC lines may enable a new level of research into the genetics and mechanisms of certain diseases that previously has not been possible due to the unavailability of primary human cardiomyocytes for functional studies. Making stem cells from the skin of adults rather than embryos also makes it much easier to create cell lines that are ethnically diverse, letting researchers better judge the safety and effectiveness of drugs on a wide range of people. As reported in 2010 by Waters (Bloomberg Business Week), Roche Holding AG scientists tracked the changes
Drug Discovery World Fall 2011
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