Regenerative medicine aims to develop effective methods to generate replacement cells from stem cells to treat diseases. It has the potential to heal damaged tissues and organs through techniques like tissue engineering and 3D bioprinting. Current therapies include skin grafts for burns and tissue-engineered bladders and blood vessels. Challenges include the difficulty obtaining stem cells, high costs, and safety issues with some methods. The future of regenerative medicine could see treatments for conditions like diabetes, heart disease, and spinal cord injuries.

1. Regenerative medicine:
Current therapies and future
directions…
•Presented By:
•Param Jyoti Rana
•Roll no-18MBC017
•PG 3rdSemester
•Department of Biochemistry
•Ravenshaw University

2. Contents:
• Introduction.
• What are stem cells???
• Different types of stem cell.
• * Embryonic stem cells
• * Adult stem cells
• What is “REGENERATIVE MEDICINE”??
• Why opt for “Regeneration”??
• The “unavoidable” faces!!
• Pioneers and the idea behind “RM”
• Induced pluripotent stem cells.
• * Responsible Genes !!
Turning Somatic Cells into Pluripotent Stem Cells
• Tissue Engineering.
Stem cell in 3D Bioprinting…
• THERAPIES IN THE MARKET.
• Pros… & Cons…
• Conclusion:
• References

3. Introduction:
• Organ and tissue loss through disease and injury motivate the development of
therapies that can regenerate tissues and decrease reliance on
transplantations.
• 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.
• Regenerative medicine, an interdisciplinary field that applies engineering and
life science principles to promote regeneration, can potentially restore diseased
and injured tissues and whole organs.
• Regenerative medicine has the potential to heal or replace tissues and organs
damaged by age, disease, or trauma, as well as to normalize congenital defects.
• 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.

4. What are stem cells???
• A stem cell is a cell with the unique ability to
develop into specialised cell types in the body.
In the future they may be used to replace cells
and tissues that have been damaged or lost due
to disease.
• Our body is made up of many different types
of cell. Most cells are specialised to perform
particular functions, such as red blood cells
that carry oxygen around our bodies in the
blood, but they are unable to divide.
• Stem cells provide have two unique properties
that enable them to do this:
1.They can divide over and over again to produce
new cells.
2. As they divide, they can change into
the other types of cell that make up the body.

5. Different types of stem cell:
• There are two main types of stem cell:
• Embryonic stem cells.
• Adult stem cells.

6. Embryonic stem cells:
• Embryonic stem
cells supply new
cells for
an embryo as it
grows and
develops into a
baby.
• These stem cells
are said to be
pluripotent, which
means they can
change into any
cell in the body.
Figure 1.2.Characteristics of Embryonic Stem Cells.
(© 2006 Terese Winslow)

7. Adult stem cells:
• Adult stem cells supply new
cells as an organism grows
and to replace cells that get
damaged.
• Adult stem cells are said to be
multipotent, which means they
can only change into some
cells in the body, not any cell,
for example:
– Blood (or 'haematopoietic')
stem cells can only replace
the various types of cells in
the blood.
– Skin (or 'epithelial') stem
cells provide the different
types of cells that make up
our skin and hair.
Winslow, Terese, and Lydia Kibiuk

8. 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.

9. Why opt for “Regeneration”??
• YESTERDAY:
• Successful transplantation
of bone, soft tissue, and
corneas occurred early in
the 20th century.
• Real progress in organ
transplantation began in
1954 with the first
successful kidney
transplant.
• During the 1960s,
successful transplantation
of pancreas/kidney, liver,
isolated pancreas and heart
occurred.
• Transplant surgery success
continued into the 1980s
with successful heart-lung,
single lung, double lung,
living-donor liver, and
living-donor lung
transplants.
TODAY
Approximately 500,000 Americans
benefit from a transplant each
year.
As of August 2010, there were
approximately 108,000 people on
the waiting list for donor organs.
Many of these individuals will die
before a suitable organ can be
found.
Tissue-engineered skin has been
used for skin replacement,
temporary wound cover for burns,
and treatment for diabetic leg and
foot ulcers.
Tissue-engineered bladder, derived
from a patient’s own cells, can be
grown outside the body and
successfully transplanted.
Tissue-engineered vascular grafts
for heart bypass surgery and
cardiovascular disease treatment
are at the pre-clinical trial stage.
TOMORROW
By providing healthy, functional tissues
and organs, regenerative medicine will
improve the quality of life for individuals.
Imagine a world where there is no donor
organ shortage, where victims of spinal
cord injuries can walk, and where
weakened hearts are replaced. This is the
long-term promise of regenerative
medicine, a rapidly developing field with
the potential to transform the treatment of
human disease through the development of
innovative new therapies that offer a
faster, more complete recovery with
significantly fewer side effects or risk of
complications.
Insulin-producing pancreatic islets could
be regenerated in the body or grown in the
laboratory and implanted, creating the
potential for a cure for diabetes.
Tissue-engineered heart muscle may be
available to repair human hearts damaged
by attack or disease.
Materials Science meets Regenerative
Medicine as “smart” biomaterials are
being made that actively participate in, and
orchestrate, the formation of functional
tissue.

10. The “unavoidable” faces!!
1st to isolate embryonic
stem cell in lab
James Thomson
1st to reprogramme cells
to form iPSCs
Shinya Yamanaka ( Nobel Prize-winning stem cell researcher)

11. 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“)
Dr. Anthony Atala

12. Pioneers and the idea behind “RM”(Contd…)
• 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.) Professor Paolo Macchiarini
Dr.Stephen Badylak

13. Pioneers and the idea behind “RM”(Contd…)
• 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.

14. Induced pluripotent stem cells:
• Induced pluripotent stem cells, or ‘iPS
cells’, are stem cells that scientists make in
the laboratory.
• ‘Induced’ means that they are made in the
lab by taking normal adult cells, like skin
or blood cells, and reprogramming them to
become stem cells.
• Just like embryonic stem cells, they are
pluripotent so they can develop into any
cell type.
• 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.

15. 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.

16. 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.
• KLF4 is involved in the regulation of
proliferation, differentiation, apoptosis and
somatic cell reprogramming.

17. Turning Somatic Cells into Pluripotent Stem Cells
• In 2006, Kazutoshi Takahashi and Shinya Yamanaka established for the first time
murine ES-like cell lines from mouse embryonic fibroblasts (MEFs) and skin
fibroblasts by simply expressing four transcription factor genes encoding Oct4,
Sox2, Klf4, and c-Myc (Figure 1) (Takahashi & Yamanaka 2006).
• They called these somatic cell-derived cell lines induced pluripotent stem (iPS)
cells. These iPS cell lines exhibit similar morphology and growth properties as ES
cells and express ES cell-specific genes. Transplantation of iPS cells into
immunodeficient mice resulted in the formation of germ-cell-tumor (teratoma)-
containing tissues from all three germ layers, confirming the pluripotent potential
of iPS cells.
• However, there were two problems: the low efficiency of establishing iPS cell lines
and some variations in gene expression profiling between iPS cells and ES cells.
The latter issue raised the concern that cell reprogramming may be insufficient to
restore full pluripotency in somatic cells as exhibited by ES cells.

18. Turning Somatic Cells into Pluripotent Stem Cells

19. Regenerative
Medicine:Current
Therapies

20. Tissue Engineering:
• In order to achieve the goals stated above, a tissue-engineered construct or tissue-
engineered medical product can only be prepared if the following three components
are available:
• 1. A scaffold or a cell carrier to house the cells and serve as their microenvironment.
• 2. Appropriate cells to fill the empty scaffold and convert it into the target tissue
• 3. Certain bioactive compounds (growth factors) to guide the cells in their attachment
• to the scaffold or during their proliferation and differentiation.
• Scaffold Forms:
• The form of the scaffold is one of the most debated issues in the tissue engineering
circles. Some researchers argue that the scaffold should not be anything more than a
sponge or foam to allow the cells to modify it as they please, while others design the
scaffolds meticulously to guide the cells toward forming the target tissue. The main
types of forms are:
• • Macroporous, foam or sponge
• • Fibrous, random or oriented
• • Lamellar or filmlike, with or without patterns or designs

21. Various 3D macroporous scaffold types. (a) Rapid prototyped (additive manufactured)
, (b) wet spun, (c) lyophilized sponge , (d) fibrous, (e) lamellar, (f) channel.
Cell seeding in scaffold

22. The Scaffold Material:
• As any biomaterial, the scaffold material can be of synthetic or biological origin
with the limitation that it should mainly be polymeric because resorbability is
essential for a successful tissue engineering application.
• The synthetic polymers used are generally condensation polymers such as
polyesters (polylactides (PLA), polyhydroxyalkanoates (PHA), polyaminoacids,
polyamides, and polyurethanes. Biological polymers are also quite frequently used
in tissue engineering.
• Among these are mainly polypeptides (collagen, gelatin, silk fibroin) and
polysaccharides (chitosan, cellulose, hyaluronan) .

23. Growth Factors:
• Growth factors are protein molecules that are
involved in the regulation of cell division,
differentiation, migration, and cell survival.
• They are growth stimulators (mitogens) and
inhibitors, act as chemotactic agents, and are
involved in angiogenesis and apoptosis.
• Growth factors are found in membrane-
bound form.
• The classical growth factor list is presented in
Table 18.3.

25. Overview :
The scheme for tissue engineering of meniscus

26. Stem cell in 3D Bioprinting…
• 3D bio printing is the process of
creating cell patterns in a confined
space using 3D printing technologies.
• 3D bio printing is the layer by layer
method to deposit materials known as
bioinks to create tissue like structure.
• Currently, bioprinting can be used to
print tissues and organs to help
research drug and pills.
• WHAT IS BIO INK???
• Bio inks are materials and it support
the adhesion, proliferation, and
differentiation of mammalian cells.
• Bio ink material is made from living
cells and it like a liquid form.
• Bio ink filaments are often deposited
at or below human body temperature
and under mild condition to preserve
bio ink printability.
BIO -PRINTER

27. Components:
Cells
Hydrogels
Bio-
printer
Bioprinted
tissue or
organs.
Pre-processing
Processing
Post-Processing
3 –PHASES:

28. THERAPIES IN THE MARKET:
• Since tissue engineering and regenerative medicine emerged as an industry about two
decades ago, a number of therapies have received Food and Drug Administration (FDA)
clearance or approval and are commercially available (Table 1).
•
(Table 1). Regenerative medicine: Current therapies and future directions
Angelo S. Maoa,b and David J. Mooneya,b,1

29. Pros… Cons…
The difficulty of obtaining stem
cells and the long period of
growth required before use.
Unproven treatments often
come with high rejection rates.
Cost can be prohibitive for
many patients
Additional ethical issues
regarding the creation of
human tissues in a lab.
Medical benefits such as
regenerating organ tissue and
therapeutic cell cloning
May hold the answer to curing
various diseases, including
Alzheimer's, certain cancers
and Parkinson's.
Research potential for human
cell growth and development to
treat a variety of ailments
Requires only a small number
of cells because of the fast
replication rate.

30. Conclusion:
• Every 30 seconds a patient dies from diseases which could be treated with
tissue replacement . A tissue engineering and regenerative medicine (TERM)
approach could probably offer the definitive solution for children
with congenital malformations, young soldiers disfigured in war and old
people suffering from chronic invalidating diseases, which are burdening
more and more heavily on world's national economies .
• This field holds the promise of regenerating damaged tissues and organs in
the body by replacing damaged tissue or organ.
• 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.

31. References:
1.Turning Somatic Cells into Pluripotent Stem Cells
By: Jiing-Kuan Yee, Ph.D. (Dept. of Virology, Beckman Research
Institute, City of Hope National Medical Center) © 2010 Nature
Education
Citation: Yee, J. (2010) Turning Somatic Cells into Pluripotent
Stem Cells. Nature Education 3(9):25
2. Hasirci, V., & Hasirci, N. (2018). Tissue Engineering and
Regenerative Medicine. Fundamentals of Biomaterials, 281–
302. doi:10.1007/978-1-4939-8856-3_18
3.3D bioprinting using stem cells, Pediatric
Research volume83, pages223–231 (2018)
Chin Siang Ong, Pooja Yesantharao, Chen Yu
Huang, GunnarMattson, Joseph Boktor, Takuma
Fukunishi, Huaitao Zhang& Narutoshi Hibino