Stem Cells: Therapeutic Applications PDF

MODULE 43 Stem Cells: Therapeutic Applications Stem cells can be used for therapeutic applications Stem Cell Therapy: Parkinson’s Disease Parkinson’s disease can be targeted by stem cell therapy, to enhance and/or replace dopamine-producing cells in the brain. Stem Cell Tissue Repair Stem cell th...

MODULE 43 Stem Cells: Therapeutic Applications Stem cells can be used for therapeutic applications Stem Cell Therapy: Parkinson’s Disease Parkinson’s disease can be targeted by stem cell therapy, to enhance and/or replace dopamine-producing cells in the brain. Stem Cell Tissue Repair Stem cell therapies capable of regenerating any human tissue damaged by injury, disease, or aging could be available within a few years, following landmark research led by UNSW Australia researchers. Stem Cell Therapy Problems many methodological difficulties need to be worked out (e.g., delivery, etc.) moral debates about embryonic stem cells: social and political implications IPS cells need more work to be effective and safe immune rejection adult stem cell problems (i.e., mutations, cancer, not as “potent”); however, if they are the patient’s own cells, then there is no immune rejection problem successes exist, such as the relatively common use of bone marrow transplantation Errors of Differentiation dysplasia – abnormal arrangement of cells, can be harmless or precursor to cancer metaplasia – conversion of one cell type to another (typically at the stem cell level), often seen with tissue damage and extensive regeneration anaplasia – loss of differentiation, typically seen in cancer it is expected that changes in gene expression accompany these alterations, some with a causative correlation Cancer Stem Cells hypothesis: most cancers are driven by a subset of cells in the tumor that have stem cell-like properties and give rise to the general mass of the tumor cancer stem cells are typically more resistant to standard cancer therapy if the bulk of the tumor is eliminated, but the cancer stem cells remain, they can cause tumor regrowth – cancer recurrence after therapy could be caused by these cells thus, the elimination of these cells is crucial for cancer therapy cancer stem cells may originate from stem cells that acquire oncogenic mutations and/or from mature cells that acquire oncogenic mutations and then dedifferentiate into cancer stem cells the dedifferentiation possibility means that all cancer cells must be eliminated, not just cancer stem cells (and the bulk of the tumor), since remaining “mature” cancer cells may reform cancer stem cells Slide 9: Likely, both transformed stem cells and transformed progenitor cells can contribute to cancer, in a context-dependent manner. Context can include tissue/organ site of cancer. Slide 10: Dedifferentiation in Colon and Stomach Cancer If you remove the cancer stem cells but leave other cancer cells behind, these other cells can dedifferentiate into cancer stem cells. Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and non-stem cells triggered by an inflammatory stroma. Thus, elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of non-stem cells that acquire tumor-initiating capacity. Therefore, data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for the dedifferentiation and generation of tumor-initiating cells in vivo. The conclusion is that the therapy needs to eliminate all types of cancer cells. MODULE 43 Dedifferentiation in Colon and Stomach Cancer Metaplastic cells in the stomach arise, independently of stem cells, via dedifferentiation or trans differentiation of chief cells. EMT and Migrating Cancer Stem Cells EMT - epithelial to mesenchymal transition MET - mesenchymal to epithelial transition EMT and MET are processes that normally occur in embryogenesis that can become “hijacked” in cancer cancer cells, possibly cancer stem cells, undergo EMT, through the action of Wnt and other cell signaling, ZEB transcription factors, SLUG, and other factors; such cells, now more mesenchymal, invasive, and non- proliferative, can metastasize to other sites, where they undergo MET, become more epithelial-like and proliferative, and form a metastatic tumor at the new site Variations in Cancer Risk among Tissues The lifetime risk of being diagnosed with: lung cancer is 6.90% colon cancer is 4.82% thyroid cancer is 1.08% stomach cancer is 0.86% cancer of the brain/nervous system is 0.6% esophageal cancer is 0.51% cancer of the small intestine is 0.20% pelvic bone cancer is 0.003% laryngeal cartilage cancer is 0.00072% Stem Cells and Aging Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Putting It Together stem cells can be used for therapeutic applications; there are some methodological difficulties, but also some successes errors of differentiation occur, some of which can lead to cancer, dysplasia, metaplasia, and anaplasia cancer stem cells can drive tumor formation, cause recurrence, be involved in metastasis (EMT/MET), and can sometimes result from dedifferentiation cancer risk is related to the number of stem cell divisions stem cells are related to aging