STEM CELL FELLOWSHIP

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1 Module I: The Basic Principles of Stem Cells 1. Basics of Stem Cells a. Understanding the development of embryonic stem cells i. Embryonic stem cells ii. Embryonic germ cells iii. Differentiated stem cell types from embryonic stem cells 1. ECTODERM: Neuroprogenitors. 2. MESODERM: Cardiomyocytes, hematopoietic progenitors, leucocytes, endothelial cells. 3. ENDODERM: Insulin positive cells, hepatocyte-like cells. 2. Principles of Stem Cells a. Understanding the principles and properties of stem cells i. Self renewal ii. Differentiation iii. Totipotency iv. Pluripotency v. Multipotency vi. Committed progenitors vii. Terminal differentiation viii. Stem cell pasticity or transdifferentiation b. Understanding the concepts of: i. Stem cell niches in bone marrow 1. Osteoblastic 2. Vascular ii. Stem cell niches in other organs, e.g. neural, cardiac, skeletal iii. Trafficking of stem cells iv. Mobilization of stem cells v. Phenotypic differentiation of stem cells 3. Principles and Understanding of: a. Adult stem cells i. Blood: Hematopoietic stem cells (HPC), endothelial stem cells (EPC) ii. Bone marrow: Hematopoietic stem cells, endothelial progenitor cells, mesenchymal stem cells. iii. Brain iv. Fat v. Liver vi. Muscle vii. Pancreas viii. Umbilical cord

2 ix. Fetal derived cells- amniotic fluid, chorionic villi, placental b. Induced pluripotent stem cells i. Autologous cell transplantation ii. Allogeneic cell transplantation iii. Issues of immune compatibility iv. Regeneration of tissues v. Development of new cellular therapies 4. Introduction to principles of Regenerative Medicine Current and future perspectives a. Rationale of cell based therapies i. Autologous cell based therapies ii. Allogeneic cell therapies iii. Immunosuppressive properties of mesenchymal stem cells iv. Commercialization of cell therapy v. Current issues in stem cell based therapies vi. Basics of cell therapy applications for: 1. Neural 2. Cardiovascular 3. Orthopedic 4. Metabolic and secretory 5. Hematopoietic and autoimmune Module II: The Biological Basis of Stem Cells in Regenerative Medicine 1. Understand the biological basis of stem cells in regenerative medicine a. Epithelial to Mesenchymal transition (EMT). b. Cellular mechanisms of the EMT. c. Changes in cell to cell adhesion. d. Cell to extracellular matrix adhesion. e. Stimulation of cell motility. f. Molecular control of the EMT. g. Signaling molecules i. TGF- pathway ii. Wnt pathway iii. Signaling by RTK ligands iv. Notch pathway h. ECM signaling i. The EMT transcriptional program. j. Cell-ECM interactions during regeneration e.g. wound healing 1. Adhesion and migration 2. Proliferation

3 3. Differentiation 4. Apoptosis k. Molecular basis of pluripotency in principles of regenerative medicine 2. Understanding of mechanisms of tissue regeneration and type of cells involved a. Compensatory hyperplasia i. Hepatocytes ii. Beta cells b. Activation of adult stem cells i. Epithelial stem cells ii. Digestive tract iii. Respiratory tract iv. Interfollicular epidermis v. Hair follicle vi. Neural vii. Kidney c. Endothelial stem cells i. Bone marrow ii. Capillaries and venules iii. Epicardium d. Hematopoietic stem cells i. Bone marrow e. Mesenchymal stem cells i. Bone marrow ii. Periosteum iii. Endosteum iv. Dental pulp v. Adipose tissue vi. Connective tissue f. Muscle stem cells i. Skeletal muscle ii. Myocardium 3. Understanding of chemical/physical induction of repair and regeneration. a. Topical agents for flair repair b. Regeneration templates c. Soluble factors d. Natural regeneration promoting and inhibitory molecules e. Small molecules 4. Understanding how cells change their phenotype a. Stem cells b. Plasticity- transdifferentiation and transdetermination c. Cell fusion

4 d. Cell phenotype e. Control of gene activity f. Extrinsic control 5. Understand basic principles of somatic cloning and epigenetic reprogramming. a. Short history of cloning b. Technical aspects of somatic nuclear transfer c. Success rates of somatic cloning d. Basic epigenetic mechanisms e. Application of somatic nuclear transfer Module III: The Principles of Stem Cell Tissue and Organ Repair: Bench to Bedside Understanding the principles of cells and tissue development. 1. Genetic approaches in human embryonic stem cells (ESC) and their derivatives. Somatic cell nuclear transfer-derived ESC 2. Embryonic stem cells: derivation and properties 3. Induced pluripotent stem cells and their current state of development for reprogramming adult cells to become pluripotent 4. Stem cells from amniotic fluid and placenta 5. Stem cells derived from cord blood 6. Multipotent adult progenitor cells 7. Bone marrow stem cells 8. Hematopoietic stem cells 9. Neural stem cells 10. Mesenchymal stem cells 11. Hepatic stem cells 12. Skeletal muscle stem cells 13. Islet and pancreatic stem cells 14. Retinal stem cells 15. Peripheral blood stem cells 16. Somatic cells: Growth and expansion potential of T lymphocytes 17. Cancer stem cells Module IV: Understanding the Principles of Therapeutic Applications of Cell Therapy Understand the principles of therapeutic applications of cell therapy. 1. Biomineralization and bone regeneration 2. Articular cartilage 3. Stem cell therapy for diabetes

5 4. Cardiovascular regeneration and neovascularization in adults with heart disease 5. Musculoskeletal repair 6. Hepatocyte transplantation 7. Neurological disorders e.g. stroke 8. Bone marrow stem cell transplantation for cancer 9. Bone marrow stem cell transplantation for autoimmune disorders 10. Bone marrow stem cell transplantation for marrow aplasia 11. Parkinson s disease and Alzheimer s disease and other neurodegenerative disorders 12. Corneal repair 13. Genitourinary system repair 14. Skin therapy 15. Peripheral nerve regeneration 16. Stem cell therapy for burn injuries 17. Stem cell therapy for baldness 18. Stem cells for retinal repair 19. Endothelial progenitor cells and clinical applications a. Transplantation of hepatic stem cells b. Potential applications for cell therapy 20. Stem cells in lung morphogenesis, regeneration and carginogenesis 21. Noninvasive imaging in stem cell therapies 22. Alimentary tract and stem cells 23. Dental tissue regeneration Understand principles of regulations and ethics as applied to stem cells 1. Ethical considerations in human tissue engineering and therapies 2. US stem cell research policy 3. FDA regulatory process 4. Issues in US patent law Module V: Clinical Case Studies of Stem cells for Blood Disorders and Chronic diseases of Aging 1. Stem cell therapy for diabetes 2. Cardiovascular regeneration and neovascularization in heart disease 3. Stem cell therapy for Musculoskeletal repair 4. Stem cell therapy for Liver Failure 5. Bone marrow stem cell transplantation for cancer 6. Bone marrow stem cell transplantation for autoimmune disorders 7. Bone marrow stem cell transplantation for marrow aplasia

6 8. Stem cell therapy for Stroke 9. Stem cell therapy for Parkinson s disease 10. Stem cell therapy for Alzheimer s disease and other neurodegenerative disorders Module VI: Stem Cells at the frontiers of Disease and Aging 1. Skin therapy 2. Peripheral nerve regeneration 3. Stem cell therapy for burn injuries 4. Stem cell therapy for baldness 5. Stem cells for retinal repair 6. Transplantation of hepatic stem cells and potential applications for cell therapy 7. Stem cells in lung morphogenesis and regeneration 8. Stem Cell Storage potential for the future

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