Cancer Stem Cell Hypothesis

Cancer stem cell hypothesis a ‘low frequency’ (somewhat controversial) cancer stem cell is responsible for cancer growth - if true, need to target/destroy these cancer stem cells or will get cancer recurrence Applications for stem cell research Help better understand development of human tissues: - what genes or proteins are involved in normal tissue development? - what genes or proteins are involved in congenital defects, disease or injury? - provide leads for finding new cures Aid new drug development: - make specialized cell types for: - drug screening for new candidate drugs - laboratory based toxicity testing to minimize toxicity testing in animals Use in regenerative medicine: - stimulate cells and tissues in the patient to re-grow or repair - grow replacement cells or tissue in the lab for transplantation (‘tissue engineering’) Novel drug discovery - high-throughput chemical screening: identify drug candidates for further testing - test toxicity of candidate new drugs: more accurate than animal testing Regenerative medicine therapies Applications: spinal injury, macular degeneration, stroke, diabetes, cartilage injury, cataract, Alzheimers, Parkinsons, etc, etc Tissue engineering therapies Transplant WSU Regenerative Medicine Human pluripotent stem cells Generate/purify LECs (can make 106-108) Use these to make >100,000 functional human micro-lenses in vitro… ABC News 19 March Investigating cataract formation, anti-cataract drugs, and lens regeneration as an improved treatment for child cataract Challenges for developing new stem cell therapies 1. Research-scale technical challenges - 2. make/purify/proliferate effector cells investigate molecular mechanisms of diseases Moving from lab-scale to production-scale 3. do small-scale techniques work at large-scale? quality assessment and quality control of cells to transplant? Overcome tissue rejection 4. are a patient’s own tissue-restricted stem cells suitable? (e.g. leukemia) - need a wide range of human embryonic stem cell lines? are patient-specific ‘reprogrammed cells’ feasible current high cost of generating reprogrammed cells time required (>3 months): suitability for acute injuries? (e.g. spinal damage) Develop appropriate clinical transplantation protocols - what cell type is needed (e.g. mature cell or a progenitor cell)? - when to transplant (e.g. early- or late-stage disease)? how many cells needed? delivery method: cell suspension or adhered to a matrix? (what matrix composition?) avoid tumour formation Current stem cell-based therapies Current most common diseases treated with stem cells: - leukemias (treated with hematopoietic stem cells) lymphomas (treated with hematopoietic stem cells) [corneal burns (limbal stem cells)] Example of hematopoietic stem cell therapy: - harvest hematopoietic stem cells (HSCs) to use in treatment HSCs used to be taken from bone marrow HSCs now ‘mobilized’ into the blood stream (via growth factors) & harvested intravenously - HSCs from umbilical cord blood also being used kill malignant cells via chemotherapy and/or radiotherapy transplant (inject) new hematopoietic stem cells autologous transplant (patient’s own cells used) allogenic transplant (donor cells used) syngeneic transplant (cells donated by identical twin) provide immunosuppression when necessary to protect against rejection Other stem cell ‘treatments’ New Scientist, 3 August 2009 Stem cell tourism – patients paying for treatment at illegal "guerrilla" clinics – continues to be a lucrative racket. Police in Hungary last week arrested individuals they suspect of running an illegal stem cell treatment clinic in Budapest. Reuters reported the police saying that the treatments were unproven, based on stem cells taken from embryos or aborted fetuses, and cost as much as $25,000 per person... Stem cell tourism BBC News, 18 February 2009 A boy treated with foetal stem cells for a rare genetic disease has developed benign tumours, raising questions about the therapy's safety. The boy, now 17, received the stem cells in 2001 at a Moscow hospital and four years later scans showed brain and spinal tumours, PLoS Medicine reports. Israeli doctors removed the abnormal growth from his spine and tests suggest it sprouted from the stem cells... Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient. Amariglio et al. 2009. PLoS Medicine. 6(2): e1000029 Conclusions: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor derived brain tumor. Further work is urgently needed to assess the safety of these therapies. Stem cell clinical trials vs unproven treatments How do clinical trials differ from the unproven stem cell ‘treatments’: - publically available data that underwent peer-review - multiple in vitro and in vivo pre-clinical studies - had to obtain approval from health regulatory body (FDA in USA) - clinical trials will evaluate the safety and then the efficacy of the therapy as a patient/physician you should always CHECK THE CLAIMS and be aware of vested interests Phase I studies assess the safety of a drug or device Phase II studies test the efficacy of a drug or device Phase III randomized & blind testing; hundreds to thousands of patients Phase IV (Post Marketing Surveillance): after a drug/device approved for consumer sale - compare against other treatments - monitor long-term effectiveness - determine cost-effectiveness - outcomes can see the drug/device restricted or taken off market 63.7% (mainly early-stage) trials reported +ve outcomes - 48 trials registered by known stem cell tourism clinics … none had reported results - reporting guidelines needed for early-phase clinical trials Resources on stem cell tourism - desperate patients - unscrupulous operators with unproven ‘treatments’ - need better patient education for better patient protection http://www.stemcellessentials.asscr.org https://www.youtube.com/watch?v=947F1Mgaji8 International Society for Stem Cell Research http://www.closerlookatstemcells.org/Home.htm Find out what's possible. Know what to ask. We have all heard about the extraordinary promise that stem cell research holds for the treatment of human diseases. Clinics all over the world claim to offer stem cell treatments for a wide variety of conditions. But are all of these treatments likely to be safe and effective? The ISSCR provides information to help you evaluate these claims.