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Stem Cell Research


Presented at Ignited By Truth Conference Raleigh, NC (February 18, 2006) ... Jacques Mistrot M.D. Can we vs. Should we? Dramatic advances of modern molecular biology ... – PowerPoint PPT presentation

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Title: Stem Cell Research

Stem Cell Research
Jacques Mistrot M.D.
Can we vs. Should we?
  • Dramatic advances of modern molecular biology and
    genetics will continue at an accelerating pace
  • We must ask the morality questions before
    attempting the can we questions?
  • We must not commit moral evil to produce moral

  • Humanitys moral capacity has not kept pace
    with its technological skill . . . contemporary
    society is truly ill.
  • Joseph Cardinal Ratzinger,
  • October 24, 2004.

Stem Cell/Cloning Topics
  • What are stem cells?
  • Possible uses of the technology
  • Current status/knowledge
  • Questions and known problems
  • Ethics, morality and Church teaching

Stem Cell Definition
  • Self renewable a cell that has the ability to
    continuously divide
  • Pluripotent ability to develop into several
    different kinds of cells/tissues
  • Repair ability to return function to damaged
    cells in the living organism

Kinds of Stem Cells
Stages of Embryogenesis
Derivation and Use of Embryonic Stem Cell Lines
ESCs Differentiate Into Different Tissue Types
Possible Uses of Stem Cell Technology
  • Repair of defective cell types (Type 1 diabetes,
    Parkinsons disease, heart disease, nerve damage)
  • Replace tissues/organs?
  • Study of embryology and diseases
  • Development of new drugs

Embryonic Stem Cells (ESCs) vs. Adult Stem
Cells (ASCs)
Sources of ESCs
  • Excess embryos from In Vitro Fertilization
  • Therapeutic Cloning
  • Induced pluripotent stem cells - iPS

In Vitro Fertilization
  • Combination of sperm and eggs in the laboratory
    to produce a zygote (embryo)
  • Multiple embryos are produced
  • Embryos are grown in the laboratory until they
    reach the 6-10 cell stage (day 2-3)
  • Embryos are implanted (usually 3-4) in the
    mothers uterus
  • Excess embryos are frozen for possible later use

Conceptualization of Therapeutic Cloning
Cloned Embryonic Stem Cells Advantages/Problems
  • Advantages
  • Minimal rejection (patients own DNA)
  • Problems
  • Only 25 of clones became embryos
  • Only 5 of embryos survived to become a cell line
  • 1 success rate (animals)
  • Embryo destroyed

Therapeutic vs. Reproductive Cloning
  • SCNT Somatic Cell Nuclear Transfer
  • The technique of nuclear transfer to a
    de-nucleated egg cell is the same for either type
    of cloning
  • The difference is the destination of the newly
    formed human life (embryo)
  • Implantation (reproductive) vs. Destruction

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Therapeutic vs. Reproductive Cloning
  • Once therapeutic cloning is legalized who
    will stop implantation ?
  • Genetic enhancement could be around the corner
    once reproductive cloning is legalized
    athletes, geniuses

Claims for ESCs UnsubstantiatedCurrent and
potential problems for ESCs
  • No current clinical treatments in humans
  • -Geron Corporation
  • Few therapy successes in animal models
  • Difficulties in obtaining pure cultures in vitro
  • Questions regarding what tissues they will
    develop into
  • Problems of immune rejection (foreign DNA)
  • Potential for tumor formation and destruction of
    normal tissue into which they are implanted
  • Ethically contentious when source is destroyed
    IVF or cloned embryos

Early Successes Adult Stem Cells
  • Human bone marrow stem cells (when exposed to
    various growth factors) turned on genes found in
    bone, cartilage, fat, muscle, blood, endothelial,
    nerve and liver cells.
  • Amnionic fluid stem cells recently shown to have
    similar traits to ESCs with less chance of
  • Umbilical cord blood promises to replace bone
    marrow as a source of stem cells with less chance
    of rejection.

Adult Stem Cells
  • Adult stem cells have been isolated from
  • amniotic fluid heart
  • peripheral blood cartilage
  • umbilical cord blood thymus
  • placenta dental pulp
  • brain tissue adipose tissue
  • muscle cornea
  • salivary gland pancreas
  • tendon liver
  • skin nasal mucosa

Ample Evidence that Adult Stem Cells show
Pluripotent Capacity
  • Adult stem cells from bone marrow can form new
    neurons in the human brain. Proceedings of the
    National Academy of Sciences USA 100, 1364-1369,
    4 Feb 2003.
  • Transplantation of adult bone marrow stem cells
    can repair patients hearts. The Lancet 361,
    45-46, 4 Jan 2003.
  • Adult stem cells from bone marrow can form all
    body tissues. Nature 418, 41-49, 4 July 2002.
  • Patients receiving adult bone marrow stem cell
    transplant stem cells also formed liver, skin,
    digestive tract. NEJM 346, 738-746, 7 March
  • A single adult mouse bone marrow stem cell can
    form functional marrow, blood cells, liver, lung,
    gastrointestinal tract, skin, heart and skeletal
    muscle. Cell 105, 369-377, 4 May 2001.
  • Adult stem cells from brain can grow into a wide
    variety of organs heart, lung, intestine,
    kidney, liver, nervous system, muscle, and other
    tissues. Science 288, 1660-1663, 2 June 2000.

Current Clinical Uses of Adult Stem Cells
  • Cancers Lymphoma, leukemias, breast, renal,
    ovarian, etc.
  • Autoimmune diseases multiple sclerosis,
    systemic lupus, rheumatoid arthritis, etc.
  • Anemias (incl. sickle cell anemia)
  • Immunodeficiencies including human gene therapy
  • Bone/cartilage deformities children with
    osteogenic imperfecta
  • Corneal scarring generation of new corneas to
    restore sight
  • Repairing cardiac tissue after heart attack
    bone marrow or muscle stem cells from patient
  • Parkinsons retinal, nasal or neural stem cells
  • Growth of new blood vessels to prevent gangrene
  • Gastrointestinal lining regenerate ulcerous
  • Skin grafts grown from hair follicle stem cells
    burns, etc.
  • Wound healing bone marrow stem cells stimulate
    skin healing
  • Spinal cord injury clinical trials currently in
    Portugal, Italy, S. Korea

Current Uses of Stem Cells
  • Adult Stem Cells ESC
  • Retinoblastoma None
  • Ovarian Cancer
  • Merkel Cell Cancer
  • Testicular Cancer
  • Lymphoma
  • Acute Lymphobolastic Leukemia
  • Acute Myelogenous Leukemia
  • Chronic Myelogenous Leukemia
  • Juvenile Myelomonocytic Leukemia
  • Angioimmunoblastic Lymphadenopathy
  • with Dysproteinemia
  • Multiple Myeloma
  • Myelodysplasia
  • Breast Cancer
  • Neuroblastoma
  • Non-Hodgkin's Lymphoma
  • Hodgkin's Lymphoma

Current Uses of Stem Cells
  • Adult Stem Cells ESC
  • Soft Tissue Sarcoma None
  • Scleromyxedema
  • Multiple Sclerosis
  • Crohn's Disease
  • Rheumatoid Arthritis
  • Juvenile Arthritis
  • Systemic Lupus
  • Polychondritis
  • Systemic Vasculitis
  • Sjogren's Syndrome
  • Behcet's Disease
  • Myasthenia
  • Red Cell Aplasia
  • Autoimmune Cytopenia
  • X-Linked Lymphoproliferative Syndrome
  • X-Linked Hyperimmunoglobuline-M Syndrome
  • Severe Combined Immunodeficiency Syndrome-X1

Current Uses of Stem Cells
  • Adult Stem Cells ESC
  • Waldenstrom's Macroglobulinemia None
  • Aplastic Anemia
  • Amegakaryocytic Thrombocytopenia
  • Chronic Epstein-Barr Infection
  • Fanconi's Anemia
  • Diamond Blackfan Anemia
  • Thalassemia
  • Stroke
  • Osteogenesis Imperfecta
  • Sandhoff Disease
  • Corneal Regeneration
  • Hemophagocytic Lymphohistiocytosis
  • Primary Amyloidosis
  • Limb Gangrene
  • Surface Wound Healing
  • Heart Damage
  • Parkinson's Disease

Adult Stem Cells Problems
  • Found in small numbers in most tissues except
    bone marrow, placenta, amnionic fluid and cord
  • Grow slowly in tissue culture
  • OCT4, NANOG genes (2005)
  • NASA micro-gravity growth technique (2005)
  • Growth factor cocktail 10x increase (2006)
  • Amnionic fluid cells grow rapidly

Adult Stem Cells Advantages
  • Promising source of treatment
  • Able to generate virtually all adult tissues
  • Can multiply almost indefinitely, providing
    numbers sufficient for clinical treatments
  • Proven success in laboratory culture
  • Proven success in animal models of disease
  • Proven success in current clinical treatments
  • Ability to home in on damage
  • Avoid problems with tumor formation
  • Avoid problems with transplant rejection (same
    person donor or good tissue-match)
  • Avoid ethical dilemma

Moral and Ethical Considerations of Stem Cell and
Cloning Research
  • Adult stem cells
  • None
  • Cloned embryonic stem cells
  • Embryo destroyed
  • Reproductive cloning is a possible result
  • Embryonic stem cells from IVF
  • Embryo must be destroyed
  • Defense of embryo destruction is based on embryos
    not being persons utilitarian philosophy

Right to Life
  • The Declaration of Independence of the United
    States guarantees certain unalienable Rights,
    that among those are Life, Liberty and the
    pursuit of Happiness

When Does Human Life Begin? Medical Embryology
  • The Developing Human Clinically Oriented
  • Zygote this cell results from the union of an
    oocyte and a sperm. A zygote is the beginning of
    a new human being (i.e., an embryo). Human
    development begins at fertilization This highly
    specialized, totipotent cell marks the beginning
    of each of us as a unique individual.

Moore and Persaud The Developing Human.
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Common Definitions of Personhood
  • Functional -
  • Self-consciousness
  • Capacity to reason
  • Capacity to communicate
  • Potentiality-
  • Arguments For Using Embryos
  • Utility -
  • Size -

Embryo Is Not a Person
  • Personality definition problems
  • What traits define personhood?
  • Who makes the definition?
  • Society has excluded certain humans from
    personhood before (e.g., African slaves, Jews,
    etc.) Should we make a new list of human

PersonhoodFunctional Embryo Is Not a Person.
. .
  • Persons . . . are members of a social community
    that shapes and values them, and personhood must
    be defined in terms of interactions and
    relationships with others.
  • Susan Sherwin. 1999. Ethical Issues Perspectives
    for Canadians. Ed. Soifer, Eldon. Peterborough,
    Ontario Broadview Press, p. 267

  • The lack of certain functional personality traits
    would remove from personhood
  • Those who are in a coma
  • Elderly with degenerative disorders (Alzheimer's,
  • Most children under 3 years old
  • Mentally deficient
  • Is is okay to consider these human beings as

  • Claim
  • Embryos are only potential life because most do
    not result in births in nature
  • Science estimates
  • Only 1/3 of natural embryos implant
  • Once implanted only 2/3 embryos survive to birth
    80 lost

Potential Life
  • Nature takes life in many ways
  • a Tsunami may take thousands of lives
  • Because life is lost through natural means is not
    the same thing as taking those lives by intent!
  • To destroy an embryo because it is only potential
    life in nature is also not justified

UtilityFrozen embryos are going to be
discarded anyway and should be used for research
to help mankind
  • Utility dictates the sacrifice of some for the
    benefit of others
  • Always arbitrary usually strong vs weak
  • Nazi experimentation was utilitarian
  • Prisoners on death row are also going to die, so
    why not do research on them?

SizeJust a small ball of cells
  • Does size defines humanness?
  • Is a teenager more human than an infant because
    of size?
  • Is a basketball player more human than a dwarf?

The Human Embryo
  • Biologically a human being
  • An integral being a self-sustaining
  • organism
  • Retains the same genetic identity
  • through all subsequent stages of
  • development
  • -from embryo to death!
  • Once, we all looked just like this!

Catholic Church Teachings
Is the Catholic Church opposed to all stem cell
  • The Church is not opposed to research involving
    adult stem cells, normally obtained from adult
    tissue, umbilical cord blood, placenta and other
    sources that pose no moral problem.

Why is the Church opposed to stem cell research
using the embryo?
  • Because harvesting these stem cells kills the
    living human embryo.
  • The Church opposes the direct destruction of
    innocent human life for any purpose, including

Is the human embryo a person?
  • By person the Church means an individual human
    being endowed with a rational and immortal human
  • Does the embryo have an immortal soul from the
    moment of conception?

Donum Vitae, I.1
  • The conclusions of science regarding the human
    embryo provide a valuable indication for
    discerning a personal presence at the moment of
    this first appearance of human life how could a
    human individual not be a human person?

  • Reason tells us that by virtue of the fact that
    the embryo is a human being, it should be
    accorded all the respect of a human person.
  • The Church teaches us that we should treat the
    embryo, from the moment of conception as if it
    were a human person.

Is the Church telling us to choose the lives of
embryos over the lives of suffering patients?
  • No. We are called to respect both, without
    discrimination . . .
  • We must help those who are suffering, but we may
    not use an evil means to justify a good end.

Non Embryo-Destructive Methods To Produce
Embryonic-Like Stem Cells
Could ES cells be generated without the
destruction of embryos?
  • Controlled nuclear reprogramming of adult cells

Nuclear Reprogramming
  • Biological rationale
  • The DNA sequence of most somatic cells (the
    cells that make up the adult organism) is
    completely identical to that of the embryo.
  • During development, no new DNA is added to our
  • Cell identity is determined by which of the
    30,000 genes are on or off.

Cloning reprogramming
  • Factors in the cytoplasm of the oocyte reprogram
    the transplanted somatic nucleus to become like
    the nucleus of an embryo.
  • Adult genes are shut off and embryonic genes are
    switched on.
  • The nucleus of the adult cell is being

Could an adult somatic cell be reprogrammed to
become a pluripotent cell, rather than an embryo?
  • Yes!
  • If ES cells are fused to somatic cells, adult
    genes are shut off and pluripotent genes are
    turned on in the somatic cell.

  • Embryonic stem cell
  • Green genes on
  • Red genes off

Hybrid cell with 2 nuclei
Nuclei fuse
Problem Hybrid cell has genes from both cells
-gt Immune mismatch
  • Stable hybrid
  • Green genes on
  • Red genes off

  • Reprogramming genes -
  • OCT 4
  • SOX2
  • LIN28

Pluripotent stem cell
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Practical Scenario
  • Patient has diabetes.
  • A skin biopsy is used to establish a culture of
    growing skin fibroblasts from the patient (no
    immune rejection possible).
  • The skin cells are manipulated with a cocktail of
    factors that result in nuclear reprogramming and
    establishment of a pluripotent stem cell.
  • The cells are expanded to a large quantity and
    then differentiated into insulin secreting
    pancreatic beta-cells.
  • The beta-cells are harvested and transplanted
    into the liver of the patient where they produce
    insulin, thereby curing the diabetes.

Nuclear Reprogramming
  • Has been done successfully in the mouse and human
  • Chance for eventual therapeutic success in humans
    is good.
  • Technology is much easier/cheaper.
  • Egg donors not needed.
  • Ethical considerations appear sound.

Thank You