Lecture_62 - Bch4122: Lecture #6 Stem Cell Treatments for...

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Bch4122: Lecture #6 Stem Cell Treatments for Skeletal Muscle Supplemental Reading: F.D. Price, K. Kuroda, M.A. Rudnicki, Stem cell based therapies to treat muscular dystrophy, BBA 1772: 272-283, 2007.
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How do you know if stem cell therapy worked? Need to: 1. Show that the stem cell has differentiated into the desired cell type 2. Show that the tissue function has been improved 3. Ensure that the appropriate model system is used 4. Ensure that no negative side-effects occurred
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Two strategies for cell based therapy to treat muscular dystrophy: Autologous stem cell transfer Allogenic stem cell transfer Muscle stem cells From patient Muscle stem cells with restored dystrophin expression Genetic alteration Re-implantation Muscle stem cells From Donor Transplantation Into patient
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Two strategies for cell based therapy to treat muscular dystrophy: Autologous stem cell transfer Allogenic stem cell transfer Derived from the patient and therefore less likely to have immune response Genetic alteration can change the stem cells and result in an immune response No genetic alteration Risk of immune rejection Requires immunosuppression and donor compatibility
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Current Sources of Stem Cells for Muscle Regeneration 3. Mesenchymal stem cells 1. Primary myoblasts from satellite cells 4. Embryonic stem cells 2. Satellite Cells 5. Mesangioblasts
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Satellite cells are quiescent until they are activated to proliferate and generate cells that either differentiate or remain satellite cells Satellite cell Myoblast Intermediate cell
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Have been used in clinical trials to treat patients with DMD with limited success Approach: To isolate satellite cells from matched donors and culture them to form primary myoblasts Repetitive intramuscular injections of large quantities of myoblasts 1. Primary myoblasts from satellite cells Muscle fibre
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Outcome of myoblast transfer Some expression of dystrophin has been restored No substantial physiological correction of the dystrophic phenotype
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Satellite Myoblast Intermediate cell Problems with myoblast transfer 1. Grafted myoblasts have limited migration and repeated local injections are required. Since heart and diaphragm are the biggest problems for DMD patients, it is currently not possible to inject muscle at 1 - 2 mm apart to ensure patient survival. 2. Transplanted myoblasts do not become satellite cells and are limited in long term repair.
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Approach: Isolate a pure population of satellite cells using a surface marker (Note: myoblasts are satellite cells that have been allowed to grow in culture) Problems: Currently difficult because we don’t have good surface markers. Will require a lot of muscle to isolate enough
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This note was uploaded on 12/18/2011 for the course BCH 4122 taught by Professor Ilonaskerjanc during the Spring '11 term at University of Ottawa.

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Lecture_62 - Bch4122: Lecture #6 Stem Cell Treatments for...

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