2. The emerging field of treatment called “regenerative
medicine” or “cell therapy” refers to treatments that are
founded on the concept of producing new cells to replace
malfunctioning or damaged cells as a vehicle to treat
disease and injury.
Our focus is the development of effective methods to
generate replacement cells from stem cells.
This is especially true of diseases associated with aging
such as Alzheimer’s disease, Parkinson’s disease, type II
diabetes, heart failure, osteoarthritis, and aging of the
immune system, known as immunosencence.
It is believed that replacing damaged or malfunctioning
cells with fully functional ones may be a useful therapeutic
strategy in treating many of these diseases and conditions.
Introduction..
3. What are stem cells???
Stem cells are the cells which are
able to self renew and
differentiate into mature cells
(potency).
Stem cells are cells that have the
ability to branch out and change,
or differentiate, into two or
more different cell types, ability
to develop into functional,
differentiated cells.
In general, there are two broad
categories of stem cells: adult
stem cells and embryonic stem
cells.
4. STEM CELL Types
Adult stem cells are derived from
various tissues in the human body.
Because they can branch out into
many different cell types, they are
referred to as “multipotent.”
Embryonic stem cells, referred to
as ES cells, which are derived from
pre-implantation embryos, are unique
because they are “pluripotent.”
It means that they can develop into
all cells and tissues in the body, and
they self-renew indefinitely in their
undifferentiated state.
5. The “unavoidable” faces!!
1st to isolate
embryonic stem cell
in lab.James Thomson
Shinya Yamanaka
1st to reprogramme
cells to form iPSCs
6. What is “REGENERATIVE MEDICINE”??
Regenerative medicine is the "process of replacing or regenerating human
cells, tissues or organs to restore or establish normal function".
First cells are
isolated. Then the isolated
cells are
manipulated
expanded and or
organs are
generated from
reprogrammed cells.
The modified
cells are
transplanted
into patients.
7. Why opt for “Regeneration”??
The shortage of organs available for
donation
Organ transplant rejection; These
unlimited supplies of autologous cells like
iPSCs could be used to generate
transplants without the risk of immune
rejection.
8. Pioneers and the idea behind “RM”
At the Wake Forest Institute for Regenerative
Medicine, in North Carolina, Dr. Anthony Atala and his
colleagues have successfully extracted muscle and
bladder cells & cultured them in molds.
Within weeks, the cells in the molds began
functioning as regular bladders which were then
implanted back into the patients' bodies.
(-"Regenerative Medicine. NIH Fact sheet 092106.doc“)
From 1995 to 1998 Michael D. West, PhD, Geron
Corporation and its academic collaborators James
Thomson at the University of Wisconsin-Madison and
John Gearhart of Johns Hopkins University that led
to the first isolation of human embryonic stem cells.
Dr. Anthony Atala
9. Pioneers and the idea behind “RM”
Dr., Stephen Badylak at the University of Pittsburgh,
developed a process for scraping cells from the lining
of a pig's bladder, decellularizing the tissue and then
drying it to become a sheet or a powder. This cellular
matrix powder was used to regrow the finger of Lee
Spievak, who had severed half an inch of his finger
after getting it caught in a propeller of a model plane.
(-Clout, Laura (2008-04-30). "'Pixie dust' helps man grow new
finger". Telegraph.co.uk. Retrieved 2010-03-19.)
In June 2008, at the Hospital Clínic de Barcelona,
Professor Paolo Macchiarini and his team, of the
University of Barcelona, performed the first tissue
engineered trachea (wind pipe) transplantation.
(-"Tissue-Engineered Trachea Transplant Is Adult Stem Cell
Breakthrough". Scientificblogging.com. 2008-11-19. Retrieved
2010-03-19.)Paolo Macchiarini
10. Pioneers and the idea behind “RM”
In 2013, Researchers have successfully
reprogrammed adult cells in a living animal for the
first time, creating stem cells that have the
ability to grow into any tissue found in the body.
Until now these stem cells, known as induced
pluripotent stem(IPS) cells, have only ever been
created in Petri dishes in the laboratory after
being removed from the animal.
However, researchers at the Spanish National
Cancer Research Centre in Madrid, Spain, were
able to create these cells in the bodies of living
mice.
STEM CELLS
11. Induced pluripotent stem cells
(also known as iPSCs) are a type of
pluripotent stem cell that can be
generated directly from adult cells.
The iPSC technology was pioneered
by Shinya Yamanaka’s lab in Kyoto,
Japan, who showed in 2006 that the
introduction of four specific genes
could convert adult cells to
pluripotent stem cells.
He was awarded the 2012 Nobel
Prize along with Sir John Gurdon "for
the discovery that mature cells can
be reprogrammed to become
pluripotent."
Induced pluripotent stem cells
In the initial 2006 study,
it was reported that only
four transcription factors
(Oct4, Sox2, Klf4, and c-
Myc) were required to
reprogram mouse
fibroblasts (cells found in
the skin and other
connective tissue) to an
embryonic stem cell–like
state by forcing them to
express genes important for
maintaining the defining
properties of ESCs.
12. Responsible GeNeS !!
Oct-3/4: it is one of the family of
octamer ("Oct“) transcription factors, and
plays a crucial role in maintaining
pluripotency.
The absence of Oct-3/4 in Oct-3/4+ cells,
such as blastomeres and embryonic stem
cells, leads to spontaneous trophoblast
differentiation.
Myc family: The Myc family of genes are
proto-oncogenes implicated in cancer.
Sox family: The Sox family of genes is
associated with maintaining pluripotency
similar to Oct-3/4, although it is associated
with multipotent and unipotent stem cells in
contrast with Oct-3/4, which is exclusively
expressed in pluripotent stem cells
Oct-3/4
Myc
Sox
14. The most well-known type of pluripotent stem
cell is the embryonic stem cell. However, since
the generation of embryonic stem cells involves
destruction (or at least manipulation) of the pre-
implantation stage embryo, there has been much
controversy surrounding their use.
Further, because embryonic stem cells can only
be derived from embryos, it has so far not been
feasible to create patient-matched embryonic
stem cell lines.
Since iPSCs can be derived directly from adult
tissues, they not only bypass the need for
embryos, but can be made in a patient-matched
manner, which means that each individual could
have their own pluripotent stem cell line.
IPSC’s
Pros & Cons..
15. OR
Cell Therapy
Cells are then
transplanted into
the patients.
Cells are isolated from
donors or other
organisms
Isolated cells are
cultured, further
manipulated and
expanded.
It’s a in vivo
treatment
17. The “Future Prospects”
The futuristic
application of
regenerative
medicine is
depicted
diagrammatically(Andrews, Wyatt (2008-
02-07). "A "Holy Grail" Of
Healing". Cbsnews.com.
Retrieved 2010-03-19.)
18. Conclusion..
This field holds the promise of regenerating damaged tissues and organs in
the body by replacing damaged tissue or organ.
iPSCs are readily being used in personalized drug discovery efforts and
understanding the patient-specific basis of disease.
In particular, the gene c-Myc is known to promote tumor growth which would
have negatively affected iPSC usefulness in transplantation therapies but now
Glis1 TF is being used.
Efforts to generate iPSCs accomplished the goal using retroviral vectors but
now plasmids & adinoviruses are used reducing mutagenesis risks.
(Charles A. Goldthwaite, Jr., Ph.D. 2010)
19. 1. French AJ, Adams CA, Anderson LS, Kitchen JR,
Hughes MR, Wood SH. Development of human
cloned blastocysts following somatic cell nuclear
transfer (SCNT) with adult fibroblasts. Stem Cells.
2008;26:485-483.
2. Byrne JA, Pedersen DA, Clepper LL, et al.
Producing primate embryonic stem cells by somatic
cell nuclear transfer. Nature. 2007;450:497-502.
3. Hurlbut WB. Ethics and embryonic stem cell
research: altered nuclear transfer as a way
forward. BioDrugs. 2007;21:79-83.
4. Meissner A, Jaenisch R. Generation of nuclear
transfer-derived pluripotent ES cells from cloned
Cdx2-deficient blastocysts. Nature.
2006;439:212-215
Bibliography..
20. I, want to express my sincere gratitude
towards our honorable principal sir, Dr.
AMIT CHAKRABARTY,our honorable vice
principle Mrs. SUDIPA CHAKRABARTY &
our other respected faculty members for
helping me make the presentation enabling
its successful completion. Last but hardly
the least I would also like to thank my
friends for their help & coordination without
whose support accomplishing such a thing
would not have been possible.
Acknowledgement.