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NIPERD Stem Cells: Potential for Therapy. Replacement parts needed for transplantation or tissue reconstruction Replacement parts needed for transplantation.

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Presentation on theme: "NIPERD Stem Cells: Potential for Therapy. Replacement parts needed for transplantation or tissue reconstruction Replacement parts needed for transplantation."— Presentation transcript:

1 NIPERD Stem Cells: Potential for Therapy

2 Replacement parts needed for transplantation or tissue reconstruction Replacement parts needed for transplantation or tissue reconstruction Tissue Engineering Tissue Engineering PROBLEMPROBLEM

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

4 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

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7  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

8 Thomson et al Science, 1998

9 Fischbachand FischbachJ. Clin. Inv. 114:1364  Self-renewal: can divide indefinitely  Can undergo asymmetric division  Retain the capacity to develop into any adult cell type

10 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

11  Diabetes 1  Neurodegenerative disorders  Myocardial infarction  Spinal cord injury  Severe liver damage  Haematological disorders  Severe eye and ear damage

12 watch.htm

13 Homoeostasis Balance of Cell Supply

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17 Figure: Measurement of ROS in SKO- and SKOM- infected MEF compared to empty vector. D indicates day hereafter

18  Maintain capacity for self-renewal  Undergo asymmetric division or development  Differentiate to limited subset of cell types

19 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 cellsTestis, Ovary (?)

20 Cancers Acute and Chronic Leukemia High-Risk Solid Tumors Hodgkin & Non-Hodgkin Lymphoma Myelodysplastic Syndrome Blood Disorders Beta Thalassemia Diamond-Blackfan Anemia, Fanconi Anemia, Severe Aplastic Anemia 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 Metachromatic Leukodystrophy Sanfilippo Syndrome Cord Blood Registry, www.cordblood.com

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22 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.

23 A Brief History of iPS Findings 2006 2007 2008 2007

24 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

25 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

26 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.

27 Adult Stem Cell Research Network, www.ascrnetwork.com

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

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32 StudyConditionInterventionStatus Safety and efficacy of autologous bone marrow stem cells in patients with spinal cord injury Spinal cord injury Autologous bone marrow derived stem cells Recruiting Mesenchymal stem cells in critical limb ischemia Critical limb ischemia Mesenchymal stem cells; Plasmalyte A Active, not recruiting Clinical trial to study the efficacy and safety of different doses of bone marrow derived mesenchymal stem cells in patients with critical limb ischemia due to Buergers disease Critical limb ischemia; Buerger’s disease Allogenic mesenchymal stem cells; Standard protocol of care Not yet recruiting Ex vivo cultured bone marrow derived allogenic MSCs in AMI Myocardial infarction Stem cells; Plasmalyte A Active, not recruiting Allogenic mesenchymal stem cells in osteoarthritis Osteoarthriti s of knee Ex-vivo cultured adult allogenic MSCs; Plasmalyte A Recruiting www.clinicaltrials.gov Stem cell clinical trials in India- Present status

33 StudyConditionInterventionStatus Safety and efficacy of autologous bone marrow stem cells for treating osteoarthritis Osteoarthritis Autologous bone marrow stem cells Enrolling by invitation Autologous mesenchymal stem cell transplant for Parkinson’s disease Parkinson’s disease Autologous bone marrow derived stem cells Active, not recruiting Safety and efficacy of autologous bone marrow stem cells for treating chronic renal failure Chronic renal failure Autologpus bone marrow stem cells Recruiting Efficacy of autologous bone marrow derived stem cell transplantation in patients with type 2 Diabetes Mellitus Type 2 Diabetes Mellitus Stem cell harvest; Angiographic transplantation of stem cells Unknown Evaluation of the role of mesenchymal stem cells in the treatment of graft versus host disease Graft vs Host disease Mesenchymal stem cell infusion Unknown www.clinicaltrials.gov

34 StudyConditionInterventionStatus Efficacy of autologous bone marrow derived stem cell transplantation in patients with Type 2 Diabetes Mellitus-2 Type 2 Diabetes Mellitus Stem cell transplantation Unknown Clinical trial on diabetic foot using peripheral blood derived stem cells for treating critical limb ischemia Diabetic foot; critical limb ischemia; leg ulcers Will receive G- CSF and peripheral blood derived mononuclear cells; G-CSF; Standard therapy Unknown Safety and efficacy of autologous bone marrow stem cells in treating spinal cord injury Spinal cord injuries Laminectomy; Intrathecal Completed Pilot study of efficacy of Lactobacillus CD2 Lozenges in preventing high-dose chemotherapy induced oral mucositis in patients undergoing hematopoietic stem cell transplantation Oral mucositis Lactobacillus CD2 lozenges Recruiting www.clinicaltrials.gov

35 StudyCondition Intervention Status Study of the monoclonal antibody CT-011 in diffuse large B-Cell lymphoma following autologous stem cell transplantation Lymphoma, Large cell, diffuse; Lymphoma, Mixed cell, diffuse; Primary Mediastinal Large B- cell lymphoma; Transformed follicular lymphoma; Relapsed CT-011Completed BMAC enhanced coronary artery bypass grafting (CABG) Congestive heart failure Harvest SmartPReP 2 BMAC system Recruiting www.clinicaltrials.gov

36 StudyConditionInterventionStatus Safety and efficacy of autologous bone marrow mononuclear cells in patients with severe critical limb ischemia Critical limb ischemia Autologous bone marrow mononuclear cells Recruiting Granulocyte colony stimulating factor (G-CSF) in acute liver failure and alcoholic hepatitis Liver failure, acute Grnaulocyte colony stimulating factor Recruiting G-CSF and erythropoetin in survival of patients with decompensated liver disease Chronic liver disease G-CSF+EPO; Placebo Recruiting Efficacy of granulocyte colony- stimulating factor and erythropoetin for patients with acute-on-chronic liver failure Acute on chronic hepatic failure Granulocyte colony stimulating factor (G-CSF) and Erythropoeitin (EPO); Placebo Recruiting www.clinicaltrials.gov

37 StudyConditionInterventionStatus Feasibility study of autologous bone marrow aspirate concentrate for treatment of CLI Arterial occlusive diseases SmartPReP2 BMAC system Active, not recruiting Safety and efficacy evaluation of two year imatinib treatment in adjuvant gastrointestinal stromal tumor (GIST) Gastrointesti nal stromal tumors Imatinib mesylate Active, not recruiting Study of NTx  -265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in acute ischemic stroke patients StrokeHuman chorionic gonadotropin (hCG), epoetin alfa (EPO); Saline Placebo Terminated, Has results REGENESIS (CA): A study of NTx TM - 265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in acute ischemic stroke patients StrokeNTx TM -265; rhCG, rEPO; Saline placebo Terminated www.clinicaltrials.gov

38 StudyConditionInterventionStatus Chemotherapy in treating patients with acute lymphoblastic leukemia and diffuse non-hodgkin’ s lymphoma Leukemia; Lymphoma Asparaginase; cyclophosphamide; cytarabine; daunorubicin hydrochloride; doxorubicin hydrochloride; etoposide; ifosfamide; mercaptopurine; methotrexate; prednisone; vincristine sulfate; conventional surgery; radiation therapy Unknown www.clinicaltrials.gov

39 hpadh@yahoo.com


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