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Stem Cell Therapy

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									STEM CELL
 THERAPY
 PRESENTED BY
  DR.GANGA.T
     JSSMC.
    MYSORE.
              Stem cells
 Rare


 Primitive   cells

 Definedby their capacity to self
 renew as well as differentiate into
 one or more mature cell types.
 Two   broad types seen:

A – embryonic stem cells

B – adult stem cells
     Embyronic stem cell
 Derived from the inner cell mass
 Pluripotent
 Can develop into more than 200
  different cells
 Differentiate into cells of the 3 germ
  cell layers
 Because of their capacity of unlimited
  expansion and pluripotency – useful in
  regenerative medicine
    Tissue or adult stem cells
 They produce cells specific to the
  tissue in which they are found
 They are relatively unspecialized
 However they are predetermined to
  give rise to specific cell types when they
  differentiate
 Eg: haematopoietic, bone marrow,
  neural
               Properties
   Self renewal - the ability to go through
    numerous cycles of cell division while
    maintaining the undifferentiated state.

   Potency – the capacity to differentiate
    into specialized cell types.
 Totipotent   stem cells -cells
 produced by the first few divisions
 of the cell . So can form any cell of
 the embryo as well as the placenta.
 Pluripotent – these cells
 differentiate into cells derived from
 the three germ cell layers.

    embryonic stem cell,
 Eg:
 embryonic germ cell and
 embryonic carcinoma cells.
 Multipotent  – these cells can
 produce cells of a closely related
 family of cells.

 Eg:haematopoeitic stem cells,
 neural and mesenchymal stem cells
 Unipotent  – these cells only
 produce one cell type., but have the
 property of self renewal which
 distinguishes them from the non
 stem cells.
  Application of stem cells
 Stem   cell research:
1. It provides an ideal model for the
  study of development of organisms
2. It replaces damaged cells of the
  body
3. It also aids in drug discovery
 Regenerative   medicine
        and
 Therapeutic issues
  Therapeutic applications of
 embryonal stem cells –ES cell
 The potential to form 200 or more cells.
 Hence used in regenerative medicine in
  cases like cardiac failure, Parkinsons
  disease, diabetes.
 These cells are being coaxed to
  differentiate into cardiomyocytes,
  neural stem cells, insulin producing cell
  and even germ cells.
         Safety concern
 Potential to form teratomas after
  transplantation
  Hence to produce pure
  differentiated cells.
 Risk of transfer of xenopathogens
    Immunological barriers
 Rejection- mediated by class 1 MHC
  and by antigen presenting cells
  harbouring the class 2 MHC antigen
 Can be overcome by generating large
  MHC homozygous ES cell banks, and
  the production of patient specific ES
  cell via Somatic Cell Nuclear Transfer.
 EScells are used as models for
 developmental biology like early
 embryonic differentiation and
 understanding the pathogenesis of
 specific genetic diseases.
    Stem cells and diseases
 The best studied stem cells are the
  haematopoietic and the male germ
  cells.
 Some of the prominent diseases treated
  include leukemia, anaemia, thallesemia
  and myelodysplastic syndrome.
 Allogenic BMT is another well known
  procedure done.
        Fetal stem cells
Haematopoietic stem cell:
 charecterised by the presence of CD 34
 - Seen in the umbilical cord and fetal
 liver
- Have a higher cloning efficiency and
 generates more progenitors than adult
 bone marrow.
- They have a huge competitive
 engraftment advantage relative to the
 adult bone marrow.
- Fetal liver is now used to treat fetuses
 having X-Linked SCID.
 Haematopoietic stem cells used in
  patients whose haematopoietic system has
  to be replaced
They are used in
1.Providing a functional immune system in a
  person with SCID.
2.Replacing a defective blood system with a
  functional one who has non malignant
  genetic disorder like sickle cell anaemia
  and thallasemia.
3.Restoring the haematopoietic system in
  cancer patients after treatment.
  Transplantation can be
1. Autologous

2. Syngeneic

3. Allogenic

GVHD is least when there is genetic
   identity.
 Other fetal cells are
 Mesenchymal stem cells-differentiate to
  bone, fat and cartilage like the adult
  counterpart.
 Neural stem cell- they differentiate into
  neurons, astrocytes and oligodendrocytes.
  They are the main source of cells for
  degenerative CNS injury for replacement.
  Eg: parkinson’s disease
     Potential application of fetal
              stem cells
     In the field of fetal medicine:
1.    Non invasive prenatal diagnosis
2.    Intrauterine stem cell
      transplantation
3.    Gene therapy
   Umbilical cord blood stem
              cells
 It has both mesenchymal blood cell
  and haematopoietic stem cells.
 1st successful umbilical cord blood
  transplantation in 1989 in a patient
  with Fanconi’s anaemia.
Haematopoeitic stem cells
 Derived  from bone marrow in adults
  and umbilical cord blood
 Option given to the parents regarding
  stem cell banking during antenatal
  visits
 25% chance that sibling also can have
  a perfect match
   Blood is collected
    from umb cord
    immediately after
    delivery about 100-
    150cc
   The number of cells in
    1 ml is 40,000
   They are stored in
    blood banks at
    -196deg celsius in a
    state of suspended
    animation and restart
    their activity on
    thawing
 Advantages over bone marrow
             cells
1.   High rate of engraftment
2.   More tolerant to tissue matches
3.   Less severe GVHD
4.   Rarely contaminated with latent virus
5.   Easy to collect, not painful
6.   Superior proliferative capacity
7.   Greater immunological naievity
8.   Unlimited supply
9.   Lower cost
    Ailments for which stem cells
        are being used now
   Acute leukemias
   Chronic leukemias
   Myelodysplastic
    syndromes
   Marrow failure
   Myeloproliferative
    disorders
   Lymphoproliferative
    disorders
 Phagocyte  disorders
 Inherited disorders like Lesch
  Nyhan syndrome, beta Thallesemia
  etc
 Inherited platelet abnormalities
 Inherited metabolic disorders like
  Mucopolysaccharidosis, Hurler’s
  syndrome, Krabbe disease,
  Niemann- pick disease etc
 Histocytic  disorders
 Inherited erythrocyte abnormalities

 Inherited immune system disorders
  like ataxia telangectesia, DiGeorge
  syndrome, SCID etc
 Plasma cell disorder

 Malignancies like neuroblastoma,
  Ewing sarcoma, Renal cell CA etc
        Trials underway
 Cardiac disease
 Diabetes
 Multiple Sclerosis
 Muscular Dystrophy
 Parkinson’s disease
 Spinal cord injury
 Stroke
 Future stem cell application
 Alzheimer’s   Disease
 Lupus

 Rheumatoid    arthritis
 Research  is going on regarding the
  use of stem cells for male infertility
  in mouse
 However the progeny has severe
  abnormalities
    Also recent research suggests that
     oocyte can be generated from
     stem cells originating from
1.   Bone marrow- haematopoietic
     stem cells
2.   Ovarian surface cells
        Ethical issues
 Are we trying to play GOD?
 Is embryo a person?

 Will stem cell research encourage
  embryo destruction and abortions?
       Guidelines for stem cell
         research in India
   Compulsory registration of the existing
    cell lines to be registered under specific
    apex bodies in the field

   Genetic research dealing with human
    egg or sperm and genetic engineering
    and then transfer of human blastocysts
    will not be allowed
 Research and therapy using
 fetal/placental stem cell will be
 allowed

 Termination of pregnancy cannot
 be sought for donating fetal tissue
 for therapeutic or financial benefits
 All the umbilical cord blood banks
  should be registered with Drug
  Controller General of India
 Research into human cloning is not
  to be done
 These guidelines are aimed to
 encourage development of sound
 research and therapy, prevent any
 misuse of human embryos and
 fetuses and protect patients from
 fraudulent treatments in the name
 of stem cell research.

								
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