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Harish Padh hpadh@yahoo.com Vice Chancellor Sardar Patel University PowerPoint Presentation
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Harish Padh hpadh@yahoo.com Vice Chancellor Sardar Patel University

Harish Padh hpadh@yahoo.com Vice Chancellor Sardar Patel University

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Harish Padh hpadh@yahoo.com Vice Chancellor Sardar Patel University

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  1. Stem Cells: Potential for Therapy Harish Padh hpadh@yahoo.com Vice Chancellor Sardar Patel University NIPERD

  2. PROBLEM Replacement parts needed for transplantation or tissue reconstruction Tissue Engineering

  3. Solution: STEM CELLS Replacement parts needed for transplantation or tissue reconstruction Tissue Engineering

  4. Stem Cells Stem cells are potentially immortal cells capable of self-renewal and also give rise to differentiated cells No area of research since gene therapy has evoked so much enthusiasm and hope

  5. Stem cells are body ‘master cells’ • Differ from mature cells which are fully committed • Stem cells are thus reserve supply of replacement cells that multiply when needed • Formed at conception & gradually become specialized • Our body retains stem cell reserves in various organs to replace diseased tissue • As the stem cell reserve gets depleted, we succumb to diseases, disorders and process of aging

  6. Embryonic Stem Cells • Longer life span, almost ‘immortal’ • High degree of plasticity – Pluripotent • Easier to isolate and cultivate • Limitless supply of cells in culture • More genetic stability • Ethical issues • Form teratomas • Will face immune rejection

  7. Embryonic Stem Cells Thomson et al Science, 1998

  8. Properties of Pluripotent Stem Cells • Self-renewal: can divide indefinitely • Can undergo asymmetric division • Retain the capacity to develop into any adult cell type Fischbachand FischbachJ. Clin. Inv. 114:1364

  9. Characterization of hES Cells Oct-4 (Pou-Transcription factor) Stage Specific Embryonic Antigens SSEA-3 SSEA-4 Tumor Recognition Antigens TRA-1-60 TRA-1-81 High Alkaline Phosphatase activity High Telomerase Activity Karyotyping

  10. Therapeutic Potential Cell transplantation therapy • Diabetes 1 • Neurodegenerative • disorders • Myocardial infarction • Spinal cord injury • Severe liver damage • Haematological disorders • Severe eye and ear damage

  11. http://www.youtube.com/watch?v=cgw19KMcWw4&feature=player_detailpagehttp://www.youtube.com/watch?v=cgw19KMcWw4&feature=player_detailpage watch.htm

  12. Homoeostasis Balance of Cell Supply

  13. EVERYDAY NEED 5 m x 1000 x 40 = 200 billion per day RBC 5000 x 1000 x 40 = 200 million per day WBC

  14. Stem Cells Embryonic Stem CellsAdult Stem Cells Figure: Measurement of ROS in SKO- and SKOM- infected MEF compared to empty vector. D indicates day hereafter

  15. Adult Stem Cells • Maintain capacity for self-renewal • Undergo asymmetric division or development • Differentiate to limited subset of cell types

  16. Adult Stem Cells - Sources Hematopoietic Fetal liver & spleen, bone marrow, peripheral blood, umbilical cord blood Liver Portal zone near bile duct Intestine Crypts Epidermal Basal layer of skin Limbal stem cells Pigmented ciliary margin Breast Epithelium Cap cells and basal layer of mammary gland Pancreas Islets and ducts Mesenchymal Bone marrow stroma, adipose tissue Tooth & Ear Placenta Germline stem cells Testis, Ovary (?)

  17. DISEASES THAT CAN BE TREATED WITH CORD BLOOD STEM CELLS Cancers Acute and Chronic Leukemia High-Risk Solid Tumors Hodgkin & Non-Hodgkin Lymphoma Myelodysplastic Syndrome Blood Disorders Beta Thalassemia Diamond-BlackfanAnemia, FanconiAnemia, Severe AplasticAnemia Sickle Cell Disease Immune Disorders Chronic Granulomatous Disease Hystiocytic Disorders Leukocyte Adhesion Deficiency Severe Combined Immunodeficiency Diseases Wiskott-Aldrich Syndrome Metabolic Disorders Krabbe Disease Hurler Syndrome MetachromaticLeukodystrophySanfilippo Syndrome Cord Blood Registry, www.cordblood.com

  18. Adult Stem Cells • Embryonic Stem Cells • IPS

  19. Induced pluripotent stem cells ? • iPS cells are a type of pluripotent stem cell from an adult somatic cell, by inducing a "forced" expression of certain genes. • iPS cells believed to be identical to natural pluripotent stem cells, such as embryonic stem cell in many respects, such as • the expression of certain stem cell genes and proteins, • chromatin methylation patterns, • embryoid body formation, • teratomas formation, • viable chimera formation, • potency and, • differentiability.

  20. A Brief History of iPS Findings 2006 2007 2007 2008 2007

  21. SOX2 This intron less gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. MYC The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement and translocation of this gene have been associated with a variety of hematopoietic tumors KLF4 Kruppel-like factor 4 Klf4 functions upstream of Nanog in ES cell self-renewal and in preventing ES cell differentiation. Klf4 interacts directly with Oct4 and Sox2 when expressed at levels sufficient to induce induced pluripotent stem cells OCT4 (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain. This transcription factor plays a role in embryonic development, especially during early embryogenesis, and it is necessary for embryonic stem cell pluripotency

  22. Why are iPS Cells Useful? • New tools for studying development • Development of disease models • Novel cell-based therapies • Patient specific iPS lines could overcome problem of immune rejection • Avoid most ethical considerations associated with hES cells iPS Fischbachand Fischbach, J. Clin. Inv. 114:1364

  23. FIRST STEM CELL CLINICAL TRIAL APPROVED BY FDA • Food and Drug Administration (FDA) had approved the first-ever clinical trial of stem cell therapy on human subjects, in 2009. • The trial, funded by the biotech company Geron, was to test a procedure to repair spinal cord damage. • The therapy involves the injection of precursor cells into the spine, where the cells will then differentiate into oligodendrocytes, the cells type that sheathes and protects the nerves of the spinal cord.

  24. CLINICAL TRIALS IN WORLD FOR FOLLOWING DISORDERS Non-Ischemic Congestive Heart Failure Chronic Obstructive Pulmonary DiseaseStem Cells Trial in Acute Ischemic StrokeCord Blood Infusion in Children with Cerebral PalsyPeripheral arterial disease (leg blood vessel disease) Severe Intermittent Claudication Poor Blood Flow to the Heart Type 1 Diabetes Type 2 DiabetesFistulas Due to Crohn's Disease Secondary Progressive Multiple Sclerosis Frailty Syndrome Adult Stem Cell Research Network, www.ascrnetwork.com

  25. Trounstonet al. BMC Medicine 2011, 9: 52

  26. Trounstonet al. BMC Medicine 2011, 9: 52

  27. Trounston et al. BMC Medicine 2011, 9: 52

  28. Trounston et al. BMC Medicine 2011, 9: 52

  29. Stem cell clinical trials in India- Present status www.clinicaltrials.gov

  30. www.clinicaltrials.gov

  31. www.clinicaltrials.gov

  32. www.clinicaltrials.gov

  33. www.clinicaltrials.gov

  34. www.clinicaltrials.gov

  35. www.clinicaltrials.gov

  36. Sardar Patel University VallabhVidyanagar Thank you! hpadh@yahoo.com