Stem cell and its clinical implication
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Transcript of Stem cell and its clinical implication
Stem Cell and Its Clinical Implications
Presented by:
DR.Mahfujun Nahar
MS Phase-A Resident
Department of Anatomy
BSMMU
Guided by
Dr. Nahid Farhana Amin
Assistant Professor
Department of Anatomy
BSMMU
Objectives
• Define stem cell
• Outline brief history of stem cell research
• Mention the types of stem cells based on potential
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
Objectives (Contd)
• Debate for and against stem cell research
• Mention the responsibilities regarding stem cell issues
Stem Cells: Definition
- unspecialized
- self renewal
- can be induced to form specific cell types
1 stem cell
Self renewal - maintains the stem cell pool
4 specialized cells
Differentiation replaces dead or damagedcells throught the life
Why self-renew AND differentiate?1 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-4Can 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
Don’t show X inactivation
Properties of stem cell….
Stem Cell Markers
c-KitOct4 (ATGCAAAT) POU Family Protein
CD34CD38
Cd44
CD133Nestin
Cells in suspension are tagged with fluorescent markers specific for undifferentiated stem cell
Labeled cells are sent under pressure through a small nozzleand pass through an electric field
A cell generates a negative chargeif it fluoresces and a positive charge if it does not.
Laser beam passes through one cell
FLUROSCENT ACTIVATED CELL SORTING
Stem cell
SEPARATION OF STEM CELL
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).
History of Stem Cell Research
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
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.
SCAN – Stem Cell Action Network
Stem Cell Research Worldwide
Global status
• Ongoing debate regarding use of embryos
• United Nations: proposal for a global policy to ban reproductive cloning only
Debate in US
• Federal funding available for research using the Bush lines onlyES 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
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
Types of Stem Cells Types of Stem Cells
based on potentialbased on potential
Types of Stem Cells based on potential
Stem cell Stem cell typetype DescriptionDescription ExamplesExamples
TotipotentTotipotent Each cell can develop Each cell can develop into a new individualinto a new individual
Cells from early Cells from early (1-3 days) (1-3 days) embryosembryos
PluripotentPluripotent Cells can form any Cells can form any (over 200) cell types(over 200) cell types
Some cells of Some cells of blastocyst (5 to blastocyst (5 to 14 days)14 days)
MultipotentMultipotentCells differentiated, Cells differentiated, but can form a number but can form a number of other tissuesof other tissues
Fetal tissue, cord Fetal tissue, cord blood, and adult blood, and adult stem cellsstem cells
This cellCan form the
Embryo and placenta
This cellCan just form the
embryo
Fully mature
Pluripotent Stem Cells more potential to become any type of cell
Multipotent stem cells
• Multipotent stem cells – limited in what the cells can become
Sources of Stem Cell
Sources of Stem Cell
• Embryonic stem (ES) cells
• Tissue (Adult) stem cells
• Induced pluripotent stem cells (iPS cells)
• Somatic cell nuclear transfer (therapeutic cloning)
Sources of stem cells
embryonic stem cells
blastocyst - a very early embryo
tissue stem cellsfetus, baby and throughout life
Embryonic stem (ES) cells:
blastocyst
outer layer of cells= ‘trophectoderm’
cells inside = ‘inner cell mass’
embryonic stem cells taken fromthe inner cell mass
culture in the labto grow more cells
fluid with nutrients
Embryonic stem (ES) cells:
embryonic stem cells
PLURIPOTENT
all possible types of specialized cells
differentiation
Tissue stem cells:
muscles
skin
surface of the eye brain
breast
intestines (gut)
bone marrow
testicles
Tissue stem cells:
MULTIPOTENT
blood stem cell
found in bone marrow
differentiation
only specialized types of blood cell:red blood cells, white blood cells,
platelets
Induced pluripotent stem cell
cell from the body
‘genetic reprogramming’= add certain genes to the cell
induced pluripotent stem (iPS) cell
behaves like an embryonic stem cell
Advantage: no need for embryos!all possible types of
specialized cells
culture iPS cells in the lab
differentiation
Induced pluripotent stem cell (Contd)
cell from the body (skin)
genetic reprogramming
pluripotent stem cell
differentiation
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
Somatic cell nuclear transfer
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
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!
Cloning
There are two VERY different types of cloning:
Reproductive cloning
Used to make two identical individuals
Very difficult to do
Illegal to do on humans
Molecular cloning
Used to study what a gene does
Routinely used in the biology labs
gene 1
gene 2
Reproductive cloning
remove nucleus and take the
rest of the cell
egg
take the nucleus (containing DNA)
cell from the body
Cloneidentical to the individual
that gave the nucleusDolly the sheep
Molecular cloning
gene 1
gene 2
2) Make a new piece of DNA
gene 1
gene 2
1) Take DNA out of the nucleus
cell 1 cell 2
gene 1 gene 2
3) Put new DNA into a test cell and grow copies
gene 1
cell divides
Daughter cells contain same DNA:
Genes 1 and 2 have
been cloned
gene 2
insert new DNA
Steps of Stem Cell Therapy
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
Steps of Stem Cell Therapy• Define the problem
Researchers want to replace dead dopamine neurons with healthy ones
• 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
Steps of Stem Cell Therapy
• Match The Stem Cell With The Recipient
Needs a good immunonlogical match.
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.
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.
Steps of Stem Cell Therapy (contd.)
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
• 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
Debate for and against stem cell
research
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.
BEFORE
AFTER
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.
Stem cell work may bypass objections
Stem-cell work may bypass objections
Stem Cell Stem Cell applicationsapplications
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
Potential uses cont.
• Biotechnology(drug discovery & development
– Safety testing of new drugs on
differentiated cell lines
– Screening of potential drugs
Potential uses cont.• Cell based therapies:
– Regenerative therapy to treat Parkinson’s, heart disease, diabetes etc
– Stem cells in gene therapy as vehicles
– Stem cells in therapeutic cloning
– Stem cells in cancer
Stem Cell ApplicationsStem Cell Applications
• Tissue repair- nerve, heart, muscle, organ, skin
• Cancers
• Autoimmune diseases
- diabetes, rheumatoid arthritis, multiple sclerosis.
Tissue Repair
• Regenerate spinal cord, heart tissue or any other major tissue in the body.
http://www.youtube.com/watch?feature=player_embedded&v=eXO_ApjKPaI
Replace Skin
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
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
Rheumatoid Arthritis
• Adult Stem Cells may be helpful in jumpstarting repair of eroded cartilage.
Type I Diabetes
• Embryonic Stems Cells might be trained to become pancreatic islets cells needed to secrete insulin.
• window to early brain development
• Identify critical genes
Down Syndrome
Diseases that are treated by stem cells are:1) Acute Leukemia• Acute Lymphoblast Leukemia (ALL)• Acute Myelogenous Leukemia (AML)• Acute Biphenotypic Leukemia • Acute Undifferentiated Leukemia2) 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)
Disorders1) Stem Cell Disorders• Aplastic Anemia (Severe)• Fanconi Anemia • Paroxysmal Nocturnal Hemoglobinuria • Congenital Cytopenia• Dyskeratosis Congenita2) Myeloproliferative Disorders• Acute Myelofibrosis • Agnogenic Myeloid Metaplasia • Polycythemia Vera • Essential Thrombocythemia3) Lymphoproliferative Disorders• Non-Hodgkin’s Lymphoma • Hodgkin’s disease • Prolymphocytic Leukemia4) Phagocyte Disorders• Chediak-Higashi Syndrome • Chronic Granulomatous Disease • Neutrophil Actin Deficiency • Reticular Dysgenesis
5) Inherited Metabolic Disorders• Mucopolysaccharidoses (MPS) • Hurler’s Syndrome (MPS-IH) • Scheie Syndrome (MPS-IS) • Hunter’s 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 • Gaucher’s Disease • Niemann-Pick Disease • Wolman Disease • Metachromatic Leukodystrophy6) Histiocytic Disorders• Familial Erythrophagocytic Lymphohistiocytosis • Histiocytosis-X • Hemophagocytosis• Langerhans’ Cell Histiocytosis
7) Inherited Immune System Disorders• Ataxia-Telangiectasia• Kostmann Syndrome• Leukocyte Adhesion Deficiency • DiGeorge Syndrome • Bare Lymphocyte Syndrome • Omenn’s 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 DisorderOther 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 • Waldenstrom’s Macroglobulinemia• AmyloidosisAbnormalities1) Inherited Platelet AbnormalitiesCongenital Thrombocytopenia2) Inherited Erythrocyte Abnormalities• Beta Thalassemia Major • Sickle Cell Disease• Blackfan-Diamond Anemia• Pure Red Cell AplasiaOther Malignancies• Ewing Sarcoma • Neuroblastoma• Renal Cell Carcinoma• Retinoblastoma• Brain tumor• Ovarian Cancer• Small Cell Lung Cancer• Testicular Cancer
Responsibilities regarding stem cell
issues
Responsibilities regarding stem cell issues
Become informed
The facts about stem cell research and its curative potential.www.stemcellfunding.org
www.stemcellaction.org
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.
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
Technical Challenges
• Source - Cell lines may have mutations
• Delivery to target areas
• Prevention of rejection
• Suppressing tumors
Mutations can lead to leukemia
Problems with Adult Stem Cells
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?rid=mboc4.figgrp.3748• http://www.news.wisc.edu/packages/stemcells/illustration.html• http://www.drugs.com/enc/images/images/en/17010.jpg• http://embryology.med.unsw.edu.au/Notes/placenta.htm• http://www.dnalc.org/stemcells.html• http://gslc.genetics.utah.edu/units/stemcells/
Thank you all