STEM CELLS

Presented by
Birendra Kumar
 Flow of the Semminar
 What is stem cells?
 classification
 Stem cell therapy
 Stem Cells transplantation
 Leukemia
 Cancer stem cells (CSC)
 CSC on Cancer Therapy
 Breast cancer & Brain Tumor
what are stem cell !!!!
Types of stem cells
 Embryonic stem cell
 Source - Excess
fertilized eggs
from IVF (in-vitro
fertilization) clinics
& Therapeutic
cloning (somatic
cell nuclear
transfer)

 Stem cells can divide
in culture to form
more of their own
kind, thereby
creating a stem
Somatic Cell Nuclear Transfer
The nucleus of a donated egg is
removed and replaced with the
nucleus of a mature, "somatic cell"
(a skin cell, for example).
No sperm is involved in this
process, and no embryo is created
to be implanted in a woman’s womb.
The resulting stem cells can
potentially develop into specialized
cells that are useful for treating
severe illnesses.
illnesses
 STEM CELLS THERAPY
• Its type of genetic medicine that introduce new
cells into damaged tissue in order to treat a
disease or injury
• medical researchers believe that stem cell
treatments have the potential to change the
face of human disease and alleviate suffering
• cancer, Type 1 diabetes mellitus,
Parkinson's disease, Huntington's disease,
cardiac failure, muscle damage and
neurological disorders
 Stem cells transplantation
• Its to replaced the Bone
marrow Stem cell as
high doges of
chemoterpic agent
is reqd. for killing
cancer cell.
• 3 types are there
• Autologous : own
donor
• Allogeneic :
receipt from
another donor
• Syngeneic : from
identical twin. (as
they’ve same set
of HLA Ag)
•
Stem Cell Therapy for
Leukemia
 The importance of self-renewal in leukemic initiation and progression.

Se lf-re n e wa l is a ke y p ro p e rt y o f b o t h n o rm a l a n d le u ke m ic s t e m c e lls . Fe we r m u t a g e n ic c h a n g e s a re re q u ire d t o

t ra n s fo rm s t e m c e lls in wh ic h t h e s e lf-re n e wa l m a c h in e ry is a lre a d y a c t ive (a), a s c o m p a re d wit h c o m m it t e d
progenitors in which self-renewal must be activated ectopically (b). In addition, self-renewing stem cells are long-lived; thus, there is an increased
chance for genetic changes to accumulate in individual stem cells in comparison with more mature, short-lived progenitors. If a committed
progenitor with limited life span acquires a genetic mutation that does not confer increased self-renewal (c), that cell will likely die or undergo
terminal differentiation before enough mutations occur to propagate a full leukemogenic program.
 Recent Research
 In 25th nov’04, A team of Korean researchers reported
that they had transplanted multipotent adult stem
cells from an umbilical cord blood to a patient
suffering from a spinal cord injury and that she can
now walk on her own, without difficulty
 On October 7, 2005 issue of The Week, University of
California researchers injected human embryonic
stem cells into paralyzed mice, which resulted in
the mice regaining the ability to move and walk four
months later
 CANCER STEM CELLS
• They are cancer cell that possess
characteristics associated with normal
stem cells, specifically the ability to give rise to
all cell types found in a particular cancer
sample
• They persist in tumors as a distinct population
and cause relapse and metastasis by giving rise
to new tumors.
• They are used in cancer treatment disease
identification, selective drug targets, prevention
of metastasis, and development of new
intervention strategies.
 CSM resists
chemoterapic
agent unlike
normal tumor
cells.
 This cells will
accumulate the
site-relapse
 Then CSM will
differentiate
Breast Cancer Stem Cells: CD44 + CD24 low Lin - B38.1 + ESA+

CD44 and CD24 – adhesion molecules

B38.1 – breast/ovarian cancer-specific marker
ESA – epithelial specific antigen

Al-Hajj, Muhammad et al. (2003) Proc. Natl. Acad. Sci. USA 100, 3983-3988
 Self-renewal Assay in NOD/SCID Mice
For solid tumors: surgical orthotopic implantation (SOI)

CD44 Expression
FACS Cell
Sorter
Single Cell
Solid Tumor Suspension CD24 Expression

Mince Surgical
(small
pieces) Implantation
Organ Specific metastasis of Breast Cancer Cells

MDA-MB-231 Breast Cancer Cell Line

Isolate Single Clonal Populations (SCPs)

Introduce Luciferase Bioluminescent Marker and GFP Fluorescence Marker

Introduce into Nude Mice by intracardiac Injection

Minn, A. J. et al. J. Clin. Invest. 2005;115:44-55

Stem Cells in the Nervous System
 Brain Tumor Stem Cells: CD133+
CD133 – neuronal stem cell marker

Brain tumor stem cells were identified from human brain tumor samples by in vitro
neurosphere assays normally used to isolate normal neural stem cells

GFAP = glial fibrillary acidic protein Singh et. al 2003 Cancer Research 63: 5821-5828.
Brain tumor stem cells were identified by intracranial transplantation of CD133+
cells into adult NOD/SCID mouse forebrain.

CD133+

CD133+ CD133-

Singh et al. 2004 Nature 432: 396-401

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