16 - March 12, 2013.docx

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University of Toronto St. George
Molecular Genetics and Microbiology
Johanna Rommens

March 12, 2013 Potential stem cell treatments – Optimal stem cell for particular tissue – in context of disease area or organ – lead to increased organ function – could be rescue of dying cells or activity or rescue or supply of a particular needed protein in some way – it may be not be Where to get stem cells? Isolate from blood; hair follicles; Applicable stem cell properties Stem cells can repopulate – regenerate itself – stem cells can restore entire organ or part of body, in THEORY Transdifferentiation – one cell can become another cell and that’s a theoretical definition – realizing this is not clear exactly how much is feasible or whether that property is contained in some stem cells – Transdifferentiation – some blood stem cells can be used to generate other organ type cells – maybe some of the data wasn’t exactly intact or firmly established, so waned in literature Do not know how transdifferentiation can be applied – exocrine components in pancreas that excrete digestive enzymes – both pancreatic cells – some redirect exocrine to endocrine – supply transcription factors – Opportunity to give autologous stem cell implanatation – using own stem cells – autologous kind of treatment – not lead to immune response – interesting opportunity if feasible Issues for stem cell development Unknown properties of stem cells – various stem cells – sometimes surprisingly difficult to grow in tissue culture – reasons: do not know proper growth factors to stimulate them; cell culture tradition is to supply growth factors, whereas stem cells need to be kept undifferentiated, whereas addiging growth factors tend to cause differentiation – for different kinds of cells, maintain undifferentiated state – can maintain cells by not supplying them with growth factors – growth factors lead cells to programmed, differentiated state – Pursuit of stem cells in pancreas Stem cell elusive in that particular organ – Pathology of disease – if want to replenish endocrine cells in pancreas – the problem that lead to the disease in the first place was an immune response, if restore cells, immune response can still be there – take aspects of pathobiology into account – adding a cell is not trivial – consequences Human reproductive cloning not acceptable in general for cloning individuals – therapeutic cloning where idea is to generate embryos that could be used for stem cells for generation of stem cells and these could be matched by immune response individuals IPS cells – generate stem cell with prominent stem cell like properties from various cells in the adult body – from fibroblasts – grow them to induce them to become pluripotent stem cells – add a number of transcription factors – can induce that cell to differentiate into state of cell that has stunning stem cell properties – behave like stem cells – whole variety of properties – shape changes – show proliferation kinetics that look like stem cells, histone modification resemble stem cells, global gene expression patterns change dramatically to reflect stem cells, produce telomerase, treat with various growth hormones and differentiation proteins – cells can constitute an entire embryo – can generate human cells quite similarly – iPS cells provide model systems – dramatic features of these particular cells – induce them to become cardiomyocetes – they beat in the dish – observe to look like neurons and various brain cells biomedical applications of human iPS cells – three different ways of use: 1. Unique resources – iPS cells from individuals with disease – unique models of disease – respresnt the disease – better than tissue culture because they’re human 2. Drug screening - ex, treatment for cardiomyocete – 3. Direct therapeutic – replenish organ that is deficient in particular cells – take out the cells that produce pluripotent stem cells – do gene therapy – restore into individual – ultimate achievement to be gained from study of these cells – MITOCHONDRIAL DISEA
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