Stem Cells Study Guide

Stem Cells In development, tissue homeostasis, disease, and regenerative medicine Overview Stem cell properties - self-renewal - differentiation capacity Stem cell types - pluripotent stem cells - tissue-restricted (‘adult’) stem cells Stem cell functions - embryonic development - tissue homeostasis - disease and treatment Emerging stem cell therapies - clinical trials vs unproven procedures - http://www.stemcellessentials.asscr.org Learning Objectives By the end of this session, you should be able to: • Contrast key characteristic features of pluripotent stem cells and tissue specific stem cells and provide at least 2 examples of each of these cells • Describe the role that tissue-specific stem cells play in tissue homeostasis for at least two organ systems. • Explain issues surrounding clinical application of emerging and unproven stem cell procedures What is a stem cell? Stem cell types and properties Pluripotent stem cells: - unlimited in vitro proliferative capacity - can make all the cells in the body: - e.g. nerves: treat spinal injury - e.g. retinal pigment epithelium: treat blindness embryonic stem cells (from donated surplus IVF embryos) - induced pluripotent stem cells (‘reprogrammed’ somatic cells) Tissue-restricted (‘adult’) stem cells: - restricted in vitro proliferative capacity - can make only one or a few specialized cell types - blood system - intestines - ocular lens - tissue homeostasis: stem cell… transit amplifying cell… effector cell Normal stem cell biology Human development It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life." Lewis Wolpert (1986) Stem cells and gastrulation Normal stem cell biology Stem cells are involved in development, homeostasis, wound healing: Totipotent cells: can make any cell in the body or placenta - e.g. zygote Pluripotent cells: can make any cell in the body - in vivo: blastocyst inner cell mass cells and epiblast cells - in vitro: human embryonic stem cells and ‘reprogrammed’ somatic cells - cells derived from hESCs are currently in clinical trial - cells derived from hiPSCs are planned for clinical trial (2014?) Multipotent stem cells: can make a range of cells in an organ - e.g., haematopoietic, and intestinal stem cells - HSCs have been used clinically for >30 years Unipotent stem cells: can only make one type of cell - e.g., lens epithelial cells Pluripotent stem cells: human embryonic stem cells (hESCs) Pros - can differentiate to any cell type - can produce disease-specific cells for study - economically viable for clinical applications Cons - ethical concerns (e.g., destruction of an embryo) - clinical use may require immunosuppression to avoid transplant rejection Pluripotent stem cells: induced pluripotent stem cells (hiPSCs) Pros - possibility of patient-specific stem cells - alternate source of disease-specific stem cells - does not require embryo destruction Cons - known differences to hESCs (critical???) - not economically viable clinically with current reprogramming methods Reprogrammed cells (i.e., hiPSCs) for clinical therapy? Comparison of stem cell properties Pluripotent stem cells: - unlimited in vitro proliferative capacity - can make all the cells in the body: - e.g. nerves: treat spinal injury - e.g. retinal pigment epithelium: treat blindness - embryonic stem cells (from donated surplus IVF embryos) - induced pluripotent stem cells (‘reprogrammed cells’) Tissue-restricted (‘adult’) stem cells: restricted in vitro proliferative capacity (can be difficult to obtain and/or maintain) - can make only one or a few specialized cell types - blood - intestines - ocular lens - tissue homeostasis: stem cell… transit amplifying cell… effector cell Multipotent haematopoietic stem cells (HSCs) - HSCs found in: bone marrow; peripheral blood; umbilical cord blood ~1 in 100,000 bone marrow cells are HSCs: at any one time many are non-dividing - BILLIONS of new blood cells are made DAILY - the stem cell’s environment (i.e., niche) regulates the stem cell behaviour