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Stem Cell Research Reagents: Future Perspectives
Sun, June 20 2010, 12:00 AM
Posted By:
Sciclips
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Currently, there are hundreds of stem cell research reagents or kits available in the market. The research reagent need for stem cell research is very dynamic in nature since the research trends, focus and approaches evolve very rapidly. The research reagent market has to evolve quickly to adapt these challenges and develop innovative tools to accelerate research accomplishments in this area. Following are few suggestions based on our observations:
Cancer stem cells: This is one of the most promising and fastest growing areas in stem cell research. Cancer stem cells have tremendous therapeutic potential and any breakthroughs in this area may ultimately help us to find innovative methods for finding cure for cancers. In order to achieve these goals, researchers need excellent cancer stem cell reagents. Reagents for the isolation of specific cancer stem cells, probes for the identification of a specific cancer stem cell, cancer stem differentiation markers, kits for the identification of cancer stem cell differentiation and transitioning of stem cells to cancer stem cells are few to name. Some of these assays are already available. The assays should be non-invasive, not any reporter based methods (such as GFP, luciferase etc.). Reporter based assays need introduction of reporter genes into stem cells. These methods can affect the physiological or genetic properties of stem cells. A reporter based method would be ideal for studying transitioning of stem cells to cancer stem cells or normal cells to cancer stem cells. Innovative tools needs to be developed in this area. For example, reporter or substrate based approaches can be developed to study the conversion of specific normal/stem cells to cancer stem cells (such as ovarian, pancreatic, breast etc). Ideally, a non-reporter based assay would be the best. Probably, a protease or kinase or metabolite or miRNA biomarker can be used for developing non-invasive detection methods (in vivo or in vitro assays). These tools will help to identify specific factor/s that trigger the conversion of normal/stem cells to cancer stem cells. This understanding will ultimately help to identify drug targets for specific cancers. The normal/stem cells expressing reporter genes (transcriptionally regulated by cancer stem cell transtioning factors) and the methods to characterize these changes will have tremendous opportunities. It may be helpful to find out a tool for characterizing the environmental or chemical or genetical factors that trigger tumor formation. Innovative cancer stem cell research reagents will accelerate cancer drug discovery efforts as well as cancer vaccines targeting cancer stem cells.
Stem cell based drug screening assays: This area needs much more scrutiny because of the lack of understanding of stem cell mutations (including iPS cells). We need to make sure that the stem cell derived cells/tissues/organs have similar genetic make-up like normal tissues (animal model studies). However, stem cells may hold the advantage in developing drug screening assays at physiological concentrations of drug targets such as GPCRs, ion channel proteins, nuclear receptors, kinases etc. In addition to this, there is a considerable demand for other stem cell based assays in drug discovery. Few examples are: i) assays to determine the efficacy of a specific compounds or drugs on cancer stem cells. ii) identification of cancer stem cell based biomarkers for monitoring the drug treatment/efficacy iii) rapid in vitro or in vivo methods for monitoring stem cell mobilization to particular organ or tissue iv) methods for characterizing epigenetic modifications that affect cancer stem cell destruction or stem cell mobilization v) in vitro or in vivo methods for the characterization of stem cell renewal. Non-invasive and non-reporter assays are ideal for these assays, which may have direct impact on pre-clinical or clinical applications of stem cells.
Stem cell DNA fingerprinting: Rapid methods for the detection of mutations in stem cells have to be developed. This is required for any clinical or drug discovery screening assays based on stem cells. Identification of "stem cell hot spots" for induced mutations may be difficult, but it can be possible by systematic genomic analysis (e.g. next generation sequencing approaches). A mutation assay complementary to Ames test may be a possibility using stem cells.
Stem cell proteomics: Characterization of stem or cancer stem cell markers is needed for research or diagnostics or therapeutic applications. However, current proteomics tools are very cumbersome and time consuming. There is a need to develop rapid methods for the identification, characterization and validation of biomarkers. This involves mass spectrometry (MS) instrumentation, sample preparation and analysis tools (including bioinformatics tools). Peptide based (bottom-up proteomics) approaches is very time consuming and comes up with uncertainty. For example, identification of a biomarker from a trypsin digested peptide mapping very laborious and even after days or weeks of data analysis positive identification of the biomarker is not guaranteed. MS methods for sequencing larger fragments (using existing MS/MS capable instruments) can be a solution for this. Using larger fragments, positive identification biomarkers are possible rather than using tryspin digested peptides. Instead of using enzymes that generate smaller peptides (e.g., trypsin, chymotrypsin, Lys-c etc), enzymes or chemicals or physical methods that generate very large fragments can be solution for this (top-down approaches). Rapid and robust methods have to be developed for the identification of novel proteomics biomarkers. For example, phosphorylation and dephosphorylation of a particular protein may occur at a particular stage of cell biological event. In order to identify these events, there is a need for rapid and robust proteomics tools. Currently used technologies have limitations and may take years to characterize these cellular events.
miRNA: MicroRNAs are becoming a powerful tool in the stem cells. miRNAs can be a marker as well as therapeutic drug targets. There is a growing need to develop innovative tools to characterize these miRNAs, develop kits for the identification of specific cancer stem cell differentiation markers. miRNAs will also have tremendous clinical diagnostics opportunities, not only for cancer detection but also for various other diseases. In addition to RT-PCR/real-time PCR methods, reporter based assays can be developed for the detection and quantitation of miRNAs; a drug screening method for miRNA targets, methods for the rapid identification miRNA regulated proteins/metabolites, which can be potential therapeutic drug targets.
Categories:
Stem Cells
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