This document discusses the history and types of stem cells and their applications in regenerative medicine. It defines stem cells as unspecialized cells that can differentiate into other cell types and self-renew. It describes the different types of stem cells based on their potency, from totipotent stem cells found in early embryos to unipotent adult stem cells. The document outlines milestones in the development of organ and cell transplantation, from early blood transfusions to modern bone marrow transplantation. It discusses the potential of stem cells to treat diseases and conditions like Parkinson's, Alzheimer's, spinal cord injury, and diabetes.

1. Gene & Cell Therapy
antonia.follenzi@med.uniupo.it
Via Solaroli,17 – Novara
Health Sciences Dept.
Tel. 0321-660674
REGENERATIVE MEDICINE

2. Definition of stem cells: stem cells are unspecialized cells that have two
defining properties: the ability to differentiate into other cells and the ability to
self-regenerate/self-renew

3. This cell
Can form the
Embryo and placenta
This cell
Can just form the
embryo
Fully
mature

4. Stem Cell Types Based on The
Ability to Differentiate
• Totipotent  all cell types. E.g.: zygote
• Pluripotent  all three germ layers. E.g.:
human embryonic stem cells
• Multipotent  many cell types. E.g.:
hematopoietic stem cells
• Unipotent  can produce only one cell
type, but have the property of self-renewal
which distinguishes them from non-stem
cells

6. POTENCY
D
E
V
E
L
O
P
M
E
N
T
Cloning
Regeneration
Induced
reprogramming
The progressive loss of potency

7. Differentiation of Human Tissue

8. Simposium Stem Cell di FKUI, ULTAH
Kalbe 40 tahun, 2 Sept.2006
Inner cell mass
Day 5 after conception

9. Adult Stem Cells: Bone Marrow

10. Plasticity of Adult Stem Cells

11. Oct3/4
Sox2
Nanog
Ecat1
Ecat8
Dppa2
Dppa3
Dppa4
Dppa5
Dnmt3l
Fbx15
Gdf3
Sox15
Fthl17
Sall4
Rex1
Utf1
Grb2
Tcl1
β-catenin
Klf4
c-Myc
Stat3
E-Ras
Induced reprogramming of mouse
cells
Takahashi & Yamanaka, Cell, 2006

12. Induced reprogramming of mouse
cells

13. Induced reprogramming of human
cells

14. Modeling human disease with iPS cells

15. Modeling human disease with iPS cells

16. Modeling human disease with iPS cells

17. Modeling human disease with iPS cells

18. Modeling human disease with iPS cells

19. Treating human disease with iPS cells

20. Self-renewal
> 20 passages
Karyotypic stability
Pluripotency
Expression of pluripotency-associated markers
In vitro differentiation
Teratoma formation
Molecular
DNA fingerprinting
Integration of reprogramming transgenes
Silencing of reprogramming transgenes
Reprogramming of gene expression profile
Reprogramming of DNA methylation profile
Criteria for defining bona fide iPS cells

21. Simposium Stem Cell di FKUI, ULTAH
Kalbe 40 tahun, 2 Sept.2006

22. Research & Clinical Applications of
Cultured Stem Cells
• Functional genomic studies  gene
therapy
• Study of biological processes 
development of the organism &
progress of cancer
• Drug discovery & development  to
see the properties of the drugs to
differentiated cells
• Cell-based regenerative therapy

24. Diseases will potentially be treated
• Parkinson's and
Alzheimer's
diseases
• Spinal cord injury
• Stroke
• Burns
• Heart disease
• Diabetes
• Muscular dystrophy
• Osteoporosis
injuries
• Cirrhosis hepatis
• Leukemia
• Sickle cell anemia
• Osteoarthritis
• Rheumatoid arthritis
• Cancer

25. Stem Cell Characteristics Make Them Good
Candidates for Cell-based Therapies
• Potential to be harvested from patients
• High capacity of cell proliferation in culture to
obtain large number of cells from a limited
source
• Ease of manipulation to replace existing non
functional genes via gene transfer methods
• Ability to migrate to host's target tissues, e.g. the
brain
• Ability to integrate into host tissue and interact
with surrounding tissue

27. Paracelsus
• The fundamental theory behind organ extract andThe fundamental theory behind organ extract and
cell therapy is the principlecell therapy is the principle
‘‘Similia Similibus curanturSimilia Similibus curantur’ or’ or ‘Like Cures Like’‘Like Cures Like’,,
as stated by Paracelsus, a Swiss physician andas stated by Paracelsus, a Swiss physician and
philosopher of the 16philosopher of the 16thth
century. Paracelsus andcentury. Paracelsus and
many other early physicians believed that the bestmany other early physicians believed that the best
way to rebuild or revitalise ill organs or ageingway to rebuild or revitalise ill organs or ageing
tissue was to use healthy living cells of the sametissue was to use healthy living cells of the same
tissue type.tissue type.

28. In 1492, Pope Innocent VIII is said to have received, at the
behest of a Jewish physician, a transfusion of the blood of
three ten year old boys, each of whom was paid a ducat and
all of whom died. Probably the blood was drawn, but was
intended to be taken orally. Indeed, there is no reliable
evidence that the sickly pope accepted the blood at all.
This story has been told and retold over the last half
millennium. It is most likely apocryphal and has the flavor
of an early urban legend in its details and its anti-Semitic and
anti-Catholic overtones.
“First Transfusion” Myth

29. Richard Lower (1631-1691)
Richard Lower is credited with performing, in 1665, the first
authentic blood transfusion (animal to animal).
He kept exsanguinated dogs alive by connecting the carotid
artery of the donor dog to the jugular vein of the recipient dog.

30. Blood Transfusion
• 1818 - James Blundell, a British obstetrician,
performed the first successful transfusion of human
Blood to a patient for the treatment of postpartum
hemorrhage.
– Using the patient's husband as a donor, he extracted a
small amount of Blood from the husband's arm and, using
a syringe, he successfully transfused the wife. Between
1825 and 1830, he performed ten documented
transfusions, five of which proved beneficial to his patients,
and published these results.

31. Karl Landsteiner
1930 Nobel Prize Laureate In 1900, Landsteiner
showed that serum from
some individuals could
agglutinate or hemolyze
the red blood cells of
certain, but not all, other
individuals. The serum of
the latter would likewise
agglutinate the red blood
cells of the former. Still
other individuals’ red cells
were unaffected by the
serum from either of these.
He named these three
different types A, B, and
C. Today these are types
A, B, and O.

32. Dr. Alexis Carrel
• In the late 19th century, the French
Nobel laureate discovered the
potentially immortal nature of cells by
keeping alive fragments of a chicken
heart 25 years after the fowl had died.

33. E. Donnall Thomas
the father of bone marrow transplantation
The spirit of a pioneer
• 1956 – The First Transplantation Between
Identical Twins was performed in Cooperstown,
New York
– Thomas reported that total body irradiation followed
by infusion of marrow from an identical twin could
result in complete remission of leukemia.

34. 1968 – First Bone Marrow Transplant
Between Siblings
In 1968, however, enough was known about the HLA
system for a transplant between siblings to occur. Dr.
Robert A. Good performed the first successful transplant
of this sort at the University of Minnesota:
- the recipient was a four-month-old boy who had inherited
severe combined immunodeficiency syndrome (“bubble boy
syndrome”) and the donor was his eight-year-old HLA-matched
sister. The disease had previously killed 11 male children in the
boy’s family.

35. 1973 – First Unrelated Bone Marrow Transplant
• Expanding knowledge of the HLA-system allowed a
team at Memorial Sloan-Kettering Cancer Center in
New York City to perform the first unrelated bone
marrow transplant in 1973 on a five-year-old patient
suffering from sever combined immunodeficiency
syndrome. The matched donor was found in Denmark
through the Blood Bank at Rigshospitalet in
Copenhagen. The patient received multiple infusions of
marrow, and after the seventh transplant, engraftment
was achieved and hematologic function became normal.

36. Dr. Thomas, wins the 1990 Nobel Prize in Physiology or
Medicine for his pioneering work in the area of organ
and cell transplantation.
October 2012 Dr Thomas died