Molecular Medicine. Stem cell therapy Gene therapy. Immunotherapy Other therapies Vaccines. Medical genomics

Transcription

1 Molecular Medicine

2 Molecular Medicine Stem cell therapy Gene therapy Tumor therapy Immunotherapy Other therapies Vaccines Genetic diagnostics Medical genomics Medication Diagnostics

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4 medicine: old desire to replace damaged tissues B0

5 B1

6 B2 - They can give rise to every cell type zygote and 8-cell embryo zygote Inner cell mass - They an give rise to every cell type, except, trophoblast tissues blastocyst inner cell mass Trophoblast cells ES cells - They can give rise a limited type of cells adult stem cells Cardiac muscle cells Skin cell - They can divide, but they are able to give rise cells identical with themselves - neurons, skeletal muscle cells, cardiac muscle cells: Neuron

7 B3 Unipotent Non-dividing Zygote is totipotent skin cell neuron pigment cell sperm cells egg cell ectoderm Germline cells zygote blastocyst gastrula brain eye totipotent Inner cell mass pluripotent multipotent blood liver mesoderm endoderm Bone marrow skin cardiac-, skeletal musle cells red blood cells alveolar cells pancreatic cells tubulue cell smooth muscle cell thyroid cells muscle

8 B4 Brain Umbilical cord blood Neural stem cell Hematopoetic stem cell Glial cells neurons Red blood cells mezenchymal Platelets White blood cells cells

9 B5

10 B6 A A A A: adult stem cells P: progenitor cells A P D: differentiated cells P P D D

11 B Mouse stem cells (1981) Martin Evans Gail R. Martin

12 In vitro fertilization Nuclear transfer B8 nucleus egg cell 5 day embryo enucleated egg donor nucleus Tissue compatibility innner cell mass (ICM) Es cells

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14 B10 adipocyte Inner cell mass neuron macrophage Blastocyst Cultured ES cells Smooth muscle cell Glial cell 1. In vivo differentiation: implanting directly to the body 2. In vitro differentiation, and then implanting to the body

15 zygote B11

16 B12 Nuclear reprogramming (epigenetic reprogramming: loose of commitment) Somatic nuclear transfer

17 B13 Reprogramming is simple, since these cells are not differentiated, but their isolation is difficult Germ line nuclear transfer

18 B17 sperm Egg cell In vitro fertilization zygote morula blastula ES cells Pluripotent stem cells Differentiated cells Transplantation

19 B18 Nucleus from a somatic cell of patient Egg cell Nuclear transfer zygote morula blastula ES cells Multipotent stem cells Differentiated cells Transplantation

20 B19 Hematopoetic stem cells Cultured stem cells Transplantation Myeloid progenitor cell Leukemia patient In the body of patients Blood cells Multipotent cells (reduced potency) Hematopoetic cells

21 Hematopoetic stem cells differentiation B20 Lymphoid progenitor cell hematopoetic Stem cell NK cell T lymphocyte Neutrophil granulocyte B lymphocyte Bazophil granulocyte Eozinophil granulocyte Monocyte Multipotent Stem cell Myeloid progenitor cell Red blood cells Platelets odipocita osteocytes Stromal cells They protect hematopoetic cells

22 Hematopoetic stem cells Use in medicine B21 (1) Bone marrow (from 1950 s): the only successful stem cell therapy - Medication: leukemia sickle cell anemia immune deficiency bone marrow damages some metabolic disorders - Unpleasant intervention - Successful if the donor and recipient are genetically similar Bone marrow (2) Umbilical blood and (3) placenta blood (new discovery): - Use: medication of the donor person decades after the isolation or the medication of relatives

23 B22

24 B23 Genetic manipulation Blastocyst Smooth- and cardiac muscle cells, endothelial cells in vitro differentiation TRANSPLANTATION Heart progenitor cells TRANSPLANTATION, in vivo differentiation Heart (embryonic or adult) Smooth- and cardiac muscle cells, endothelial cells

25 B24 Burn injuries: Traditional treatment skin transplantation from undamaged body parts, success, since stem cells are located directly under the epidermis. If there were not enough skin, the patient could die. Since 20 years cultivation of skin stem cells Discovery of new skin stem cells in deeper layers of skin and in hair bulbs epidermis dermis hypodermis

26 Neural stem cells (NSC) - B25 neurogenesis in adult brain SVZ SVZ Olfactory bulb NSC NSC New neurons hippocampus cerebellum hippocampus HUMAN BRAIN RAT BRAIN Anterio-lateral chamber subventricular zone (SVZ)

27 B26 Parkinson s disease - Those neurons that are responsible for the elimination of unnecessary movements, are degenerated at the substantia nigra implantation of stem cells has not been proven to be successful

28 B27 Spinal cord damage Broken bone Spinal cord damage

29 B29 Éva Mezey Y chromosome

30 B30 BLOOD CELLS ADIPOCYTE EPIHELIAL CELL CARDIAC MUSCLE NEURON GLIAL CELL Stromal (mesenchymal) stem cells in the marrow

31 B32 5 day embryo STOP

32 B31 Stromal cells Mesenchimal stem cells (MSC; stromal stem cells) -Not only structural role, but a role in tissue regeneration, too. Sources: - Bone marrow, umbilical cord blood, fat tissue Doubts: it is possible that stromal cells only fused with other cell types instead of differentiating to other cell types. MSC: mesenchymal stem cells = marrow stromal cells

33 Singapore - Biopolis B33

34 He changed the stem cell law at the very first 24 hrs B33

35 B34 Basic research: Medical research: Medicine: generation of knock-out animals drug tests medication: - Testing the cells of sick patients - Leukemia, Parkinson- and disease, neural damage, seizure, cardiac disease, diabetes Real applications: - Leukemia, skin regeneration, heart attack

36 B14 Cell reprogramming Mouse ips cells (2005) Transfer of fibroblast cells to feeder cells Transformed cells Delivery of ips factors-encoding genes by retrovirus vector Shinya Yamanaka ips cells Skin fibroblast cells Some cells are transformed to ips cells ipsc: induced Pluripotent Stem Cells

37 B15 Cell reprogramming ipsc: induced Pluripotent Stem Cells

38 What and how to deliver? 36 András Nagy Somatic cells Transcription factors Integrating virus Non-integrating vector Excisable vector Protein Small molecules

39 Transcription factors 37 Pluripotent cell Multipotent cell Differentiated cell

40 B28 Genetic improvement by homologous recombination