The p53 is a tumor suppressing proteins that activates DNA repair proteins and apoptosis pathways
in response to DNA damages that are not irreparable. Mutations in p53, which affects its activity, are responsible
for developing various cancers; 83% of tumors have alterations or defect in p53 (1). The p53 plays crucial role in
embryonic stem (ES) cells. p53 represses the expression of Nanog, a transcription that is critical for the self-renewal
of ES cells (2). Loss of p53 reduces spontaneous differentiation and apoptosis in human embryonic stem cells (3).
It has been proposed that breast cancer tumors can originate from cancer stem cells or cancer cells become stem cells
due to p53 deficiency, which favors the expansion of cancer stem cells (4). Recent reports (shown below in boxes) have
shown the importance of p53 in various stem cell states. Independent studies from five laboratories have shown that
loss ofp53 is needed for the induction of induced pluripotent stem cells (iPS cells) from adult cells (see thumbnails).
The role of p53 in cancer stem cells has been shown by a recent study . This study has shown that loss of p53 induces
symmetric cell division in breast cancer stem cells and this favors breast cancer tumor growth (see thumbnails).
Categories:
Stem Cells
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The existence of cancer stem cells have started as a hypothesis and followed by enormous number of experimental evidences. Still, a large number of scientists in stem cell areas and other research areas are very skeptical about the existence of cancer stem cells. We can believe the existence of cancer stem cells and its role in cancer from all the reported studies on the isolation/characterization of cancer stem cells in various cancers such as leukemia, breast cancer, ovarian cancer, lung cancer, liver cancer, colon cancer etc from past and ongoing research on cancer stem cell. The PubMed searches on cancer stem cells showed more than 5000 articles as of October 2009 and this data indicates that the first research article on cancer stem was published on 1976 (see the box to see all the PubMEd search results). It is evident that the concept of cancer stem is known to us for more than 23 years. If the scientist would have accepted the existence of cancer stem cells a decade ago, possibly we would have been in a better position in finding a cure for cancer or may be closer to achieve this goal? May be the concept of stem cells were not established at that time?
Categories:
Stem Cells
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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.
Categories:
Stem Cells
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In recent years, there is a considerable push in adopting stem cell based assays as a drug discovery tool. The major argument behind this initiative is stem cells can differentiate into specific cell types, which can be used for targeted drug screening. Major pharmaceutical companies and public funded academic institutes have been started investing significant amount of effort and money on stem cell based drug discovery with the hope that this approach will ultimately provide real breakthroughs in drug discovery research as well as significant cost savings. There is no doubt that stem cells may offer unique opportunities in drug discovery, but the scientific data to support this notion may not yet well established to the extent that is applicable to drug discovery screening.
A most popular application of stem cells is the use of stem cell derived cardiomyocytes as a screening tool for testing cardiac toxicity of drugs. One can argue that there is enough scientific evidence to prove that stem cell differentiated cells are genetically similar to corresponding normal cells and can be used as a drug screening tool. This may or may not be true based on answers to following questions. a) can stem cells be a better tool in drug screening assays than currently used cell/animal based assays? b) are stem cell derived cell/tissue types are genetically and physiologically identical to the desired natural cell types, for example cardiomyocytes? c) are these proposed stem cell based assays will provide better tools to reduce or eliminate fatal side effects of drugs, e.g. cardiotoxicity? It is important to note that current use of cell based assays (non-stem cell based) failed to reduce or prevent fatal side effects of drugs. Based on this, it is hard to argue that currently proposed stem cell based assays provide any better solution to current problems. We need to understand genetic and physiological make up of stem cell derived cell types before we adopt this technology for making life saving decisions. In any means, our opinion does not imply that stem cell based products are not suitable for developing drug discovery assays. Our goal is to critically analyze the scientific rational behind current approaches.
Categories:
Stem Cells
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