An Overview of Stem Cell Technology to get an overall understanding of the Stem Cell World and paving the way to further research.

1. Stem Cells – An Overview
Subhajit Hazra* [02]
Department of Pharmacology
Gupta College of Technological Sciences
Asansol – 713301 ; WB.

2.  Chronology of Stem Cell Research
 Stem Cell Introduction
 Classification & Age of stem Cells
 A Brief Review on the 4 major Kinds of Stem Cells
 Induced Pluripotent Stem Cells – A Short Study
 Cloning in context of Stem Cells
 The Question - Are We Alone ?
 Chimera and its Implications
 Cancer Stem Cells
 Noble Laureates of Stem Cell Research
 Stem Cell Application
 Strategies for transplantation of Stem Cells
 Clinical Trials Undertaken in Stem Cell Research
 Ethical Considerations'
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3. James Alexander Thomson
Is an American developmental biologist
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4. 1868 — The term “stem cell” appears in scientific literature, when German biologist Ernst Haeckel.
June 1, 1909 — Russian academic Alexander Maximow lectures at the Berlin Hematological Society on a theory that all
blood cells come from the same ancestor cell. This introduces the idea of blood stem cells
1981 — Two scientists, Martin Evans of the University of Cambridge and Gail Martin of the University of California, San
Francisco, conduct separate studies and derive pluripotent stem cells from the embryos of mice
1998 - Researchers first extract stem cells from human embryos
2001 - President Bush restricts federal funding for embryonic stem-cell research
2002 - Juvenile Diabetes Research Foundation International creates $20 million fund-raising effort to support stem-cell
research.
Dec. 10, 2003 — George Q. Daley and his team publish findings on converting stem cells from mice into germ cells and,
eventually, primitive sperm cells that are able to fertilize egg cells.
2004 - Harvard researchers grow stem cells from embryos using private funding.
May 19, 2005 — South Korean scientists under the direction of Woo-Suk Hwang announce that they’ve used therapeutic
cloning to create 11 stem cell lines.
Aug. 25, 2006 — Japanese scientists Shinya Yamanaka and Kazutoshi Takahashi announce the creation of rodent induced
pluripotent cells (iPS cells).
November/December, 2007 — Three independent teams in Japan, Wisconsin and Boston, led by Shinya Yamanaka,
James Thomson, and George Q. Daley, respectively, announce that they have created human iPS cells.
Aug. 6, 2008 – The Stem Cell Program at Boston Children’s Hospital announces the creation of 10 disease-specific lines
of iPS cells.
2010 - A person with spinal injury becomes the first to receive a medical treatment derived from human embryonic stem
cells as part of a trial by Geron of Menlo Park, California, a pioneering company for human embryonic stem
cell therapies.
History of Stem Cell Research
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5. Stem Cell History Cont.
2012 Another Nobel - Yamanaka wins a Nobel prize for creating induced pluripotent stem cells,
which he shares with John Gurdon of the University of Cambridge.
2013 Therapeutic cloning - Shoukhrat Mitalipov at the Oregon National Primate Research Center
in Beaverton and his colleagues produce human embryonic stem cells from fetal cells using
therapeutic cloning – the breakthrough falsely claimed in 2005.
2014 Pre-embryonic state - Charles Vacanti of Harvard Medical School together with Haruko
Obokata at the Riken Center for Developmental Biology in Kobe, Japan, and colleagues
announced a revolutionary discovery that any cell can potentially be rewound to a pre-
embryonic state – using a simple, 30-minute technique.
2014 Therapeutic cloning – with adult cells
Teams led by Dieter Egli of the New York Stem Cell Foundation and Young Gie Chung from
CHA University in Seoul, South Korea, independently produce human embryonic stem cells
from adult cells, using therapeutic cloning. Egli’s team use skin cells from a woman with
diabetes and demonstrate that the resulting stem cells can be turned into insulin-producing
beta cells. In theory, the cells could be used to replace those lost to the disease.
AND THE LIST STILL GROWS ....
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6. What makes stem cells so valuable?
Cell Therapy
Research
New Drugs
Pluripotent
stem cells
Tissue stem
cells
No one stem cell type fits all applications.
Research must continue using all types of stem cells. 6

7. Stem Cell – Definition
• A cell that has the ability to continuously divide and
differentiate (develop) into various other kind(s) of
cells/tissues
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8. Stem cells can:
• Self-renew to make
more stem cells
• Differentiate into a
specialized cell type
Embryonic stem cells (pluripotent)
Stem cells that can become
many types of cells in the body
are called Pluripotent.
Tissue stem cells (multipotent)
Stem cells that can become
only a few types of cells are
called Multipotent.
Why are Stem Cells Special?
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9. This cell
Can form the
Embryo and placenta
This cell
Can just form the
embryo
Fully mature
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Classification of Stem Cells

10. Age of Stem Cells
Stem cell
type Description Age
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
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11. Kinds of Stem Cells & their Origin
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12. Embryonic Stem Cells
• Derived from donated IVF
embryos
• Can be grown indefinitely in
the laboratory in an
unspecialised state
• Retain ability to specialise
into many different tissue
types – know as Totipotent.
• Can restore function in
animal models following
transplantation
Human embryonic stem cells can become any cell in the
body including these beating heart cells
A Embryonic Stem Cell
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Blastocyst

13. 8-cell blastocystfertilised
egg
2-cellegg
Day 0 Day 1 Day 2 Day 3 Day 6
• Donated excess IVF (in vitro fertilization)embryos
Images from www.advancedfertility.com
Where do embryonic stem cells come from?
Inner cell mass
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14. Foetal Stem Cell
3 Sources of Foetal Stem Cells :
Trophoblast Stem Cells (TS Cells)
(Discovery that led to the successful lab culcure of TS Cells is Fibroblast Growth factor 4 –
Required to maintain TS Cells at Undifferentiated State)
Premodial Stem Cells (Embryonic Stem Cells)
Are Pluripotent in nature
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15. Umbilical Cord Stem Cells
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16. What’s in ?
• Also Known as Wharton’s Jelly
• Adult stem cells of infant origin
• Isolated prior to/ immediately following birth
• Haematopoietic stem cells (Majority)
• 100,000 Pluripotent or Multipotent stem cells per mL in UCB
• Alternate to bone marrow stem cells
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17. Types divided in:
Three important functions of UCS cells:
- Plasticity: Potential to change into other
cell types like nerve cells
- Homing: To travel to the site of tissue
damage
- Engraftment: To unite with other tissues
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18. Applications
• Hematopoietic cell transplantation (HCT) - Is curative for
malignant and nonmalignant diseases like aplastic anemia,
leukemias, metabolic and other congenital disorders.
• HLA (Human leukocyte antigen) mismatch may be better
tolerated in the UCBT (Umbilical cord blood transplantation)
setting than Bone Marrow Transplantation.
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19. Tissue Stem Cells
• Often known as Adult Stem Cells
• They are Unipotent
• Also includes stem cells isolated from fetal and cord blood
• Reside in most tissues of the body where they are involved in
repair and replacement
• Generally very difficult to isolate
• Already used to treat patients (haematological malignancies,
diseases of the immune system)
Bone marrow Kidney Lungs
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20. Induced Pluripotent Stem Cells
(IPSC’s)
• Derived from adult cells in
2007 - very recent discovery!
• Can be grown indefinitely in
culture in an undifferentiated
state
• Similar properties to
embryonic stem cells as can
differentiate into many
different tissue types –
Pluripotent
• Can create stem cells directly
from a patient for research
Induced change in
gene expression
Pluripotent
stem cells
Starting cells from
donor tissue
iPS Cells
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21. Cloning
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22. Cloning
Cloning means making an organism identical to another.
Production of one or more individual plants or animals(whole/in
part) that are genetically identical
In nature :- Identical Twins
Occurs naturally in single celled organisms
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23. Types of Cloning
Embryo Cloning
Reproductive cloning
Therapeutic Cloning
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24. Therapeutic cloning (research cloning) is when stem cells are
extracted to grow into a piece of human tissue which is encouraged
to grow into a human organ for transplant
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25. Human Stem Cells
Are We Alone ?
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26. Plant Stem Cells ?
• They are
undifferentiated cells
• Located in root
meristem, shoot
meristem, and vascular
meristem
• Create all differentiated
cell types
• Self-renew,
In this microscopy of root
meristem, the stem cells are
located within zone 1
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27. Chimera ?
A chimera is a single organism composed of cells from different zygotes.
Types of Chimera :
 Animal Chimera
 Plant Chimera
 Human to Animal Chimera (Of most impact to the society)
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Animal Chimera
Human to Animal Chimera

29. Implication of Human to Animal
Chimera
 Researchers are pursuing a number of strategies to
make pigs into human-organ donors that could cause
an immune response in primates.
The advantage of chimaeras as said by Izpisua
Belmonte is that researchers could one day use a
patient’s own cells to create a pig chimaera with a
human organ that has been grown for that individual.
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30. Cancer Stem Cells
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31. Cancer stem cells
Rare cells within tumors with the ability to self-renew
and give rise to the phenotypically diverse tumor cell
population to drive tumorigenesis
Normal stem cells
Rare cells within organs with the ability to self-renew
and give rise to all types of cells within the organ to
drive organogenesis
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32. Therapeutic implications of Cancer Stem Cells
• Most therapies fail to consider the difference in drug sensitivities of cancer stem cells
compared to their non-tumorigenic progeny.
• Most therapies target rapidly proliferating non-tumorigenic cells and spare the
relatively quiescent cancer stem cells.
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33. Future Directions
- Need to characterize cancer stem cells at the single cell level
- Understand the genetic and biochemical mechanisms that
control the self-renewal phenotype, asymmetric subdivision,
and the role of the stem cell niche in regulating the biological
properties of both normal and cancer stem cells.
- Characterize the response of cancer stem cells to
chemotherapeutic regimens.
- Develop therapeutic strategies to target cancer stem cells to
prevent tumor recurrence.
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34. Nobel Prize Winning Experiments
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35. Stem Cells Applications
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36. Strategies for transplantation of
Stem Cells
1.Undifferentiated or partially differentiated stem cells may be injected
directly in the target organ or intravenously.(i.e Hematopoietic stem
cells)
2. Stem cells may be differentiated ex vivo prior to injection into the target
organ. (Beta cells, Cardiomyocyte)
3. Growth factors or other drugs may be injected to stimulates endogenous
stem cell populations.
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42. Key Ethical Issues
• Use of fetal tissue is ethically controversial because it is
associated with abortion, which many people object to.
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43. References
 Mitalipov S, Wolf D (2009). "Totipotency, pluripotency and nuclear reprogramming". Adv. Biochem. Eng.
Biotechnol. Advances in Biochemical Engineering/Biotechnology. 114: 185–99.
 Bubela T, Li MD, Hafez M, Bieber M, Atkins H (2012). "Is belief larger than fact: Expectations, optimism
and reality for translational stem cell research. BMC Med. 10: 133.
 Oh Young Banga, Eun Hee Kim, Jae Min Cha, Gyeong Joon Moon (2016). Adult Stem Cell Therapy for
Stroke: Challenges and Progress. J Stroke > Volume 18(3).
 Simona Delia Nicoară, Sergiu Șușman, Oana Tudoran, et al. (2016), “Novel Strategies for the Improvement
of Stem Cells’Transplantation in Degenerative Retinal Diseases,” Stem Cells International, vol. 2016.
 Alan Trounson and Courtney McDonald (2015). Stem Cell Therapies in Clinical Trials: Progress and
Challenges, Cell Stem Cell 17, July 2.
 Strain, Lisa; John C.S. Dean; Mark P. R. Hamilton; David T. Bonthron (1998). "A True Hermaphrodite
Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization". The New England Journal of
Medicine. 338 (3): 166–169.
 Jun Wu et al. (2017) Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell 168, 473–486.
 Irma Virant-Klun & Martin Stimpfel (2016). Novel population of small tumour-initiating stem cells in the
ovaries of women with borderline ovarian cancer. Scientific Reports 6, Article number: 34730.
 Ran Lu et al. (2017)Neurons generated from carcinoma stem cells support cancer progression. Signal
Transduction and Targeted Therapy 2, Article number: 16036.
 Wei Guo, Joseph L Lasky and Hong Wu (2006). Cancer Stem Cells. Pediatric Research (2006) 59, 59R–
64R.
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