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Title: Stem cell and medical application


1
Stem Cell and Its Clinical Implications
2
  • Presented by
  • DR.Mahfujun Nahar
  • MS Phase-A Resident
  • Department of Anatomy
  • BSMMU

3
  • Guided by
  • Dr. Nahid Farhana Amin
  • Assistant Professor
  • Department of Anatomy
  • BSMMU

4
Objectives
  • Define stem cell
  • Outline brief history of stem cell research
  • Mention the types of stem cells based on
    potential

5
Objectives (contd)
  • Outline the sources of stem cell
  • Explain the steps of stem cell therapy
  • Discuss the health problems that might be treated
    by stem cells

6
Objectives (Contd)
  • Debate for and against stem cell research
  • Mention the responsibilities regarding stem cell
    issues

7
Stem Cells Definition
  • - unspecialized
  • - self renewal
  • can be induced to form specific cell types

8
Why self-renew AND differentiate?
1 stem cell
4 specialized cells
1 stem cell
Differentiation replaces dead or damaged cells
throught the life
Self renewal - maintains the stem cell pool
9
Properties of stem cell.
Clonogenic, a single ES cell gives rise to a
colony of genetically identical cells, which
have the same properties as the original
cell Expresses the transcription factor
Oct-4 Can be induced to continue proliferating or
to differentiate Lacks the G1 checkpoint in the
cell cycle ES cells spend most of their life
cycle in S phase Dont show X inactivation
10
Stem Cell Markers c-Kit Oct4 (ATGCAAAT) POU
Family Protein CD34 CD38 Cd44 CD133 Nestin
11
SEPARATION OF STEM CELL
Cells in suspension are tagged with fluorescent
markers specific for undifferentiated stem cell
Stem cell
FLUROSCENT ACTIVATED CELL SORTING
Labeled cells are sent under pressure through a
small nozzle and pass through an electric field  
Laser beam passes through one cell  
A cell generates a negative charge if it
fluoresces and a positive charge if it does not.
12
History of Stem Cell Research
13
History of Stem Cell Research
  • In 1998, James Thomson isolated stem cells from
    the inner cell mass of the early embryo.
  • In 1998, John Gearhart derived human embryonic
    germ cells from fetal gonadal tissue (primordial
    germ cells).

14
History of Stem Cell Research (Contd)
  • 1999 - First Successful human transplant of
    insulin-making cells from cadavers
  • 2001 - President Bush restricted federal funding
    for embryonic stem-cell research

15
History of Stem Cell Research (Contd)
  • 2004 - Harvard researchers grow stem cells from
    embryos using private funding.
  • Asia, Japan, South Korea and Singapore is moving
    forwards on stem cell research.

16
Stem Cell Research Worldwide
17
Global status
  • Ongoing debate regarding use of embryos
  • United Nations proposal for a global policy to
    ban reproductive cloning only

18
Debate in US
  • Federal funding available for research using the
    Bush lines only
  • ES cell lines from 8/9/01
  • Disadvantage of Bush stem cell lines
  • may have mutations or infections
  • Private companies continue to pursue stem cell
    research
  • therapeutic cloniing mainly

19
Stem cell research in other countries
  • Great Britain
  • Therapeutic cloning , use of excess embryos
    creation of embryos allowed
  • France
  • Reproductive and therapeutic cloning banned
  • Germany
  • Use of excess embryos and creation of embryos
    banned

20
  • Types of Stem Cells
  • based on potential

21
Types of Stem Cells based on potential
Stem cell type Description Examples
Totipotent Each cell can develop into a new individual Cells from early (1-3 days) embryos
Pluripotent Cells can form any (over 200) cell types Some cells of blastocyst (5 to 14 days)
Multipotent Cells differentiated, but can form a number of other tissues Fetal tissue, cord blood, and adult stem cells
22
Pluripotent
Multi- potent
Fully mature
23
Pluripotent Stem Cells more potential to become
any type of cell
24
Multipotent stem cells
  • Multipotent stem cells limited in what the
    cells can become

25
Sources of Stem Cell
26
Sources of Stem Cell
  • Embryonic stem (ES) cells
  • Tissue (Adult) stem cells
  • Induced pluripotent stem cells (iPS cells)
  • Somatic cell nuclear transfer (therapeutic
    cloning)

27
Sources of stem cells
tissue stem cells fetus, baby and throughout life
embryonic stem cells blastocyst - a very early
embryo
28
Embryonic stem (ES) cells
29
Embryonic stem (ES) cells
embryonic stem cells
PLURIPOTENT
30
Tissue stem cells
skin
muscles
31
Tissue stem cells
blood stem cell
differentiation
found in bone marrow
only specialized types of blood cell red blood
cells, white blood cells, platelets
MULTIPOTENT
32
Induced pluripotent stem cell

Advantage no need for embryos!
33
Induced pluripotent stem cell (Contd)
genetic reprogramming
pluripotent stem cell
cell from the body (skin)
34
  • Somatic cell nuclear transfer
  • A nucleus from an adult donor cell is inserted
    into a recipient egg cell from which the nucleus
    has been removed
  • The resulting cell is then stimulated to divide
    as a zygote later forming embryo genetically
    identical to the adult donor cell

35
Somatic cell nuclear transfer
36
  • Goals of therapeutic cloning
  • Use embryo as source for ES cells
  • Use ES cells to generate an organ with genetic
    markers identical to the patient
  • Correct genetic error in ESC in blastula stage

37
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38
Pitfalls of therapeutic cloning
  • Large number of eggs needed for SCNT
  • To harvest large number of eggs
  • excessive hormone treatment may induce high rate
    of ovulation
  • will carry species-specific mitochondrial genes
  • Mixing species is reason for concern!

39
Cloning
There are two VERY different types of cloning
40
Reproductive cloning
41
Molecular cloning
42
Steps of Stem Cell Therapy
43
Steps of Stem Cell Therapy
  • Defining the problem
  • Finding The Right Type of Stem Cell
  • Match The Stem Cell With The Recipient
  • Put the stem cells in the right place
  • Make The Transplanted Stem Cells Perform

44
Steps of Stem Cell Therapy
  • Define the problem
  • Researchers want to replace dead dopamine
    neurons with healthy ones

45
Steps of Stem Cell Therapy
  • Finding The Right Type of Stem Cell
  • Blastocyst stem cells?
  • At the time, unable to differentiate into
    neurons
  • Fetal stem cells?, Excellent candidates, ethical
    problems
  • Adult stem cells?, Hard to get, too little known

46
Steps of Stem Cell Therapy (contd.)
  • Match The Stem Cell With The Recipient
  • Needs a good immunonlogical match.

47
Steps of Stem Cell Therapy (contd.)
  • Put the stem cells in the right place
  • Surgical procedure usually required.
  • Small holes drilled in the skull, cells injected
    with a needle.

48
Steps of Stem Cell Therapy (contd.)
  • Make The Transplanted Stem Cells Perform
  • There was no guarantee how the transplanted
    cells would behave. If they did not respond to
    the proper signals from their environment, they
    might have malfunctioned or died.

49
Cell Culture Techniques for ESC
  • Isolate transfer of inner cell mass into
    plastic culture dish that contains culture medium
  • Cells divide and spread
  • Inner surface of culture dish is typically coated
    with mouse embryonic skin cells that have been
    treated so they will not divide

50
  • This coating is called feeder layer
  • provide ES cells with a sticky surface for
    attachment and release nutrients
  • There are methods for growing embryonic stem
    cells without mouse feeder cells
  • ES cells are removed gently and plated into
    several different culture plates

51
Debate for and against stem cell research
52
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53
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54
Pro-choice people
  • Utilitarianism- destruction of smaller group
    for the sake of a larger group is justifiable.
  • lead to significant information about the cause,
    new treatment possibilities, and potential cure
    for many diseases.

55
AFTER
BEFORE
56
Opinions against stem cell research
  • Stem cells are taken from a human blastocyst,
    which is then destroyed. This amounts to
    murder.
  • There is a risk of commercial exploitation of
    the human participants in ESCR.

57
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58
Stem cell work may bypass objections
59
Stem-cell work may bypass objections
60
Stem Cell applications
61
Potential Uses of Stem Cells
  • Basic research clarification of complex events
    such as
  • Molecular mechanisms for gene control
  • Role of signals in gene expression
    differentiation of the stem cell
  • Stem cell theory of cancer

62
Potential uses cont.
  • Biotechnology(drug discovery development
  • Safety testing of new drugs on differentiated
    cell lines
  • Screening of potential drugs

63
Potential uses cont.
  • Cell based therapies
  • Regenerative therapy to treat Parkinsons, heart
    disease, diabetes etc
  • Stem cells in gene therapy as vehicles
  • Stem cells in therapeutic cloning
  • Stem cells in cancer

64
Stem Cell Applications
  • Tissue repair
  • nerve, heart, muscle, organ, skin
  • Cancers
  • Autoimmune diseases
  • - diabetes, rheumatoid arthritis, multiple
    sclerosis.

65
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66
Tissue Repair
  • Regenerate spinal cord, heart tissue or any other
    major tissue in the body.

67
Replace Skin
http//www.youtube.com/watch?featureplayer_embedd
edveXO_ApjKPaI
68
Heart Disease
  • Adult bone marrow stem cells injected into the
    hearts are believed to improve cardiac function
    in victims of heart failure or heart attack

69
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70
Leukemia and Cancer
  • Leukemia patients treated with stem cells emerge
    free of disease.
  • Stem cells have also reduces pancreatic cancers
    in some patients.

Proliferation of white cells
71
Rheumatoid Arthritis
  • Adult Stem Cells may be helpful in jumpstarting
    repair of eroded cartilage.

72
Type I Diabetes
  • Embryonic Stems Cells might be trained to become
    pancreatic islets cells needed to secrete
    insulin.

73
Down Syndrome
  • window to early brain development
  • Identify critical genes

74
Diseases that are treated by stem cells are 1)
Acute Leukemia Acute Lymphoblast Leukemia
(ALL) Acute Myelogenous Leukemia (AML) Acute
Biphenotypic Leukemia Acute Undifferentiated
Leukemia 2) Chronic Leukemia Chronic
Myelogenous Leukemia (CML) Chronic Lymphocytic
Leukemia (CLL) Juvenile Chronic Myelogenous
Leukemia (JCML) Juvenile Myelomonocytic
Leukemia (JMML)Syndromes Myelodysplastic
Syndromes Amyloidosis Chronic Myelomonocytic
Leukemia (CMML) Refractory Anemia (RA)
Refractory Anemia with Excess Blasts (RAEB)
Refractory Anemia with Excess Blasts in
Transformation (RAEB-T) Refractory Anemia
with Ringed Sideroblasts (RARS)
75
Disorders 1) Stem Cell Disorders Aplastic
Anemia (Severe) Fanconi Anemia Paroxysmal
Nocturnal Hemoglobinuria Congenital
Cytopenia Dyskeratosis Congenita 2)
Myeloproliferative Disorders Acute
Myelofibrosis Agnogenic Myeloid Metaplasia
Polycythemia Vera Essential Thrombocythemia 3)
Lymphoproliferative Disorders Non-Hodgkins
Lymphoma Hodgkins disease Prolymphocytic
Leukemia 4) Phagocyte Disorders Chediak-Higashi
Syndrome Chronic Granulomatous Disease
Neutrophil Actin Deficiency Reticular
Dysgenesis
5) Inherited Metabolic Disorders
Mucopolysaccharidoses (MPS) Hurlers Syndrome
(MPS-IH) Scheie Syndrome (MPS-IS) Hunters
Syndrome (MPS-II) Sanfilippo Syndrome
(MPS-III) Morquio Syndrome (MPS-IV)
Maroteaux-Lamy Syndrome (MPS-VI) Sly Syndrome,
Beta-Glucuronidase Deficiency
Adrenoleukodystrophy Mucolipidosis II (I-cell
Disease) Krabbe Disease Gauchers Disease
Niemann-Pick Disease Wolman Disease
Metachromatic Leukodystrophy 6) Histiocytic
Disorders Familial Erythrophagocytic
Lymphohistiocytosis Histiocytosis-X
Hemophagocytosis Langerhans Cell Histiocytosis
76
7) Inherited Immune System Disorders
Ataxia-Telangiectasia Kostmann Syndrome
Leukocyte Adhesion Deficiency DiGeorge
Syndrome Bare Lymphocyte Syndrome Omenns
Syndrome Severe Combined Immunodeficiency
SCID with Adenosine Deaminase Deficiency
Absence of T B Cells SCID Absence of T
Cells, Normal B Cell SCID Common Variable
Immunodeficiency Wiskott-Aldrich Syndrome
X-Linked Lymphoproliferative Disorder Other
Inherited Disorders Lesch-Nyhan Syndrome
Cartilage-Hair Hypoplasia Glanzmann
Thrombasthenia Osteopetrosis
Adrenoleukodystrophy Ceroid Lipofuscinosis
Congenital Erythropoietic Porphyria Sandhoff
Disease
9) Plasma Cell Disorders Multiple Myeloma
Plasma Cell Leukemia Waldenstroms
Macroglobulinemia Amyloidosis Abnormalities 1)
Inherited Platelet Abnormalities Congenital
Thrombocytopenia 2) Inherited Erythrocyte
Abnormalities Beta Thalassemia Major Sickle
Cell Disease Blackfan-Diamond Anemia Pure Red
Cell Aplasia Other Malignancies Ewing Sarcoma
Neuroblastoma Renal Cell Carcinoma
Retinoblastoma Brain tumor Ovarian Cancer
Small Cell Lung Cancer Testicular Cancer
77
Responsibilities regarding stem cell issues
78
Responsibilities regarding stem cell issues
  • Become informed
  • The facts about stem cell research and its
    curative potential.
  • www.stemcellfunding.org
  • www.stemcellaction.org

79
Responsibilities regarding stem cell
issues(contd.)
  • Inform others
  • Contact patient and community groups and offer
    to give a presentation like this one. Organize a
    house party to help spread the word.
  • Collect email addresses of supporters to be added
    to mailing list.

80
Responsibilities regarding stem cell issues
(contd.)
  • Inform others
  • Arrange to meet with your political
    representatives to discuss their support for stem
    cell research
  • Find other like-minded people and work together
  • Invite friends, colleagues, and caretakers of
    patients to become involved

81
Technical Challenges
  • Source - Cell lines may have mutations
  • Delivery to target areas
  • Prevention of rejection
  • Suppressing tumors

82
Problems with Adult Stem Cells
Mutations can lead to leukemia
83
REFERENCES
  • Stem cells in class Badran, Shahira Bunker Hill
    Community College, 2007, Boston Museum of Science
    Biotechnology Symposium
  • Stem cells Cloning Stem cells Cloning David
    A. Prentice, Benjamin Cummings, 2003
  • http//stemcells.nih.gov/info/scireport/2001report
    .htm
  • http//www.ulb.ac.be/sciences/biodic/biodic/images
    /bio_animale/embryologie/fecondation/baefec_01_01.
    jpg
  • http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmboc
    4.figgrp.3748
  • http//www.news.wisc.edu/packages/stemcells/illust
    ration.html
  • http//www.drugs.com/enc/images/images/en/17010.jp
    g
  • http//embryology.med.unsw.edu.au/Notes/placenta.h
    tm
  • http//www.dnalc.org/stemcells.html
  • http//gslc.genetics.utah.edu/units/stemcells/

84
  • Thank you all
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