Recent Advances in the Clinical Applications of Stem Cells

Recent Advances in the
Clinical Applications of
Stem Cells
Dr. Boenjamin Setiawan, Ph.D.
Chairman Stem Cell and Cancer
Institute

Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D.
Indonesia, 2 Febr 2008

National
Insitute of
Health
Guidelines
for Stem Cell
Research
@ 2006 Terese
Winslow


Countries colored in brown represent about 3.5 billion people, more
than half the world's population. All have a permissive or flexible
policy on human embryonic stem cell research and all have banned
human reproductive cloning.


World Stem Cell Research Centers


Mengapa ABG penting??
1. Akademi adalah sumber SDM terdidik dan
sumber IPTEK
2. Selama dana pemerintah utk R&D kecil maka
sebaiknya Fokus pd IPTEK Teraplikasi
3. Bisnis adalah tempat untuk mengkonversi
IPTEK menjadi produk praktis yang bermanfaat
untuk masyarakat
4. Government adalah KATALISATOR untuk
menciptakan peraturan yang kondusif untuk
INOVASI melalui R&D
5. ABG harus membentuk kerjasama yang
terintegrasi secara “SEAMLESS”
6. Budaya saling mempersulit harus diubah
menjadi BUDAYA SALING
Indonesia, MEMBANTU=GOTONG ROYONG
2 Febr 2008

The Human Body
 Consist of 12 Organ Systems
 Consist of 220 types of Tissues
 Consist of 50-100 trillion cells
 Consist of 100 billion neurons
 Consist of 46 chromosomes (22 pairs and
x and y chromosomes)
 Consist of 30.000 genes
 Consist of 3,2 billion base pairs

50-100 Trillion Cells form the
Building Block of the Human Body


DNA, the genetic code is principally
found in the Nucleus of each cell


Consequently DNA is double stranded that
wound round each other in a double helix


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

Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676


Stem Cells
are taken
from the
Inner Cell
Mass at
the
blastocyst
stage and
cultured in
Simposium Asosiasi Sel Punca
dr.Boenjamin Setiawan,Ph.D.
a Petri disk

Adult Stem Cells: Bone Marrow


Plasticity of Adult Stem Cells


Therapeutic cloning


Stem Cell Banking
 Cord
 Blood banking is now becoming popular
for autologous as well as for allogeneic donor
 Adult Peripheral Blood collection and
cryopreservation can also be used for future
diseases
 Stem cells can be collected from UCB,
Adipocytes and Peripheral Blood by Apheresis
 Stem cells can be Cryopreserved for use in

Cancers, CAD, Stroke, Diabetes, Burns, Spinal
Cord injury, Osteoarthritis, Regenerative
medicine, etc.

Target Diseases for Stem Cell Therapy
Blood Diseases
 Bone marrow transplants (BMT) are a well known clinical
application of hematopoietic stem cell (HSC) therapy
 HSCs can regenerate all of the different cell types in blood
 BMT is used for the treatment of blood cancers like leukemia
and lymphoma, as well as breast cancer and any other
disease requiring immune system regeneration


 The cardiovascular
circulatory system’s main
role is to transport
nutrients and oxygen to
the 50-100 trillion cells
that makes up our body
and remove the waste
material from the body.
 The most prevalent disease
that affects the CVS is:
1. Atherosclerosis
2. Hypertension
3. Acute myocardial infarction
Indonesia, 2 Febr 2008 4. Stroke

Heart Disease
 ES cells can be induced to form cardiac muscle cells that
actually beat in culture
 When transplanted into damaged hearts, these cells can
form gap junctions and contract in unison with
surrounding cells
 HSCs can also be grafted into damaged heart muscle and,
in this new environment, are reprogrammed to produce
heart cells instead of blood cells


Arteriosclerosis, Thrombosis, and Vascular Biology.
2003;23:1185.)
© 2003 American Heart Association, Inc

Brief Review
Endothelial Progenitor Cells
Mobilization, Differentiation, and Homing
Mihail Hristov; Wolfgang Erl; Peter C. Weber
From the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten,
Ludwig-Maximilians-Universität, München, Germany


Pediatric Research 59:26R-32R (2006)
© 2006 International Pediatric Research Foundation,Figure 1. EPCs are bone marrow-
Inc.
DOI: 10.1203/01.pdr.0000203553.46471.18 derived cells that contribute to
postnatal angiogenesis. EPCs
(seen in purple at A) can be
mobilized from the bone marrow
stroma by various growth
factors and exit through
sinusoidal vessels. Once in the
bloodstream (B), EPCs begin to
differentiate (indicated by the
color change). Subsequently,
these cells home to sites of
angiogenesis in capillary beds
(C) and attach to the
endothelium. Unknown
mechanisms drive endothelial
precursors (red) to incorporate
into the endothelial wall or pro-
angiogenic monocytes (blue) to
locate behind the endothelial
wall and support the stability
and viability of the local
Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. endothelium by paracrine
mechanisms

Figure 3. Mechanism of EPC homing and differentiation. Recruitment and
incorporation of EPCs into ischemic tissue requires a coordinated multistep
process including mobilization, chemoattraction, adhesion, transmigration,
migration, tissue invasion, and in situ differentiation. Factors that are proposed to
regulate the distinct steps are indicated


 To
Prevent
Athero-
sclerosis
 Control

cholestero
l level
 Control
Hypertens
ion
 Exercise
 Diet

 No
dr.Boenjamin Setiawan,Ph.D. smoking

Differentiation of embryonic
cells into the cardiac lineage


Physiol. Rev. 85: 1373-1416, 2005; doi:10.1152/physr “Cardiac Stem Cells and
Mechanisms of Myocardial Regeneration”


Therapeutic Potential of EPC in AMI
 Figure 2. Therapeutic
potential of EPCs.
Intracoronary infusion of
EPCs in patients with
AMI may have the
potential to restore
myocardial function to
the damaged area.

 EPC transplantation
increases left ventricular
ejection fraction (LVEF),
coronary blood flow
reserve, and myocardial
viability and decreases
left ventricular end-
systolic volume
Indonesia, 2 Febr 2008 (LVESV).66

 Major Role CNS:
The main role of the nervous
system is to relay electrical
signals through the body. The
nervous system directs
behaviour and movement and,
along with the endocrine
system, controls physiological
processes such as digestion,
circulation, etc.
 The most prevalent diseases
that affect the CNS is Stroke,
Parkinson’s disease,
Alzheimer’s disease, ALS
and Autism

Proposed Mechanism for Stem
Cells in Neurodegenerative
Diseases
 Implanted stem cells migrated &
integrated extensively throughout the
brain
 Some of the transplanted cells replaced
damaged nerve cells and transmitted
nerve impulses integrate electrically
and functionally into a diseased brain
 stem cells employ multiple mechanisms 
not just cell replacement - which
collaborate to benefit disease et al, Nature 2007
Simposium Asosiasi Sel Punca Lee

Brain Cell Transplantation
 The identification and localisation of neural stem cells,
both embryonic and adult, has been a major focus of
current research.
 Potential targets of neural stem cell transplants
 1. include stroke, 2. spinal cord injury,
and
 3. neurodegenerative diseases such as
Parkinson's Disease, 4. Alzheimer
 Stem cells can provide dopamine - a chemical lacking in
victims of Parkinson's Disease
 Over 250 patients have already been transplanted with
human fetal tissue

Brain and Spinal Cord
Injury
 Neural stem cells can be
isolated from adult brains or
generated from ES cells in
culture
 HSCs can also be
transplanted into the brain
where they are
reprogrammed to generate
neurons and glial cells
 Potential applications
include Parkinson’s disease,
ALS, Huntington’s disease,
stroke, Alzheimer’s disease,
paralysis
 AnimalFebr 2008 Punca
Simposium Asosiasi Sel early human
Indonesia, 2
and dr.Boenjamin Setiawan,Ph.D.

trials are underway

Ischemic
Stroke


 Cerebral
Hemorrh
age


Spinal Cord Injuries
Hwang Mi-Soon: South
Korea

Paralyzed 19 years

Multipotent adult stem cells
injected
into her spinal cord

Currently: debilitating pain

Published in 2005 (Cytotherapy)

Parkinson’s Disease :
Degeneration of brain cells
 Cells in the
substantia nigra

 Loss of the
chemical
dopamine

 No clear
reason why

Osteoarthritis and Autoimmune
Diseases
 Mesenchymal
stem cells are
used to be
inserted into the
synovial cavity
where they
transdifferentiate
into
chondroblasts
and form new
cartilage

Osteoarthritis of the Knee Joint
 Mesenchymal stem
cells are implanted
into a
biodegradable
scaffold and
inserted into the
synovial cavity
where they will
transdifferentiate
into new cartilage

Type 1 Diabetes

 Patients lack pancreatic
beta cells and cannot
produce insulin
 Insulin-producing
structures similar to
pancreatic islets have been
generated from mouse ES
cells in culture
 It may also be possible to
isolate pancreatic stem
cells from adult tissue
 Early stage of development

Stem Cell Banking
 Cord
 Blood banking is now becoming popular for
autologous as well as for allogeneic donor
 Adult Peripheral Blood collection and
cryopreservation can also be used for future
diseases
 Endothelial progenitor cells and Mesenchymal
stem cells are potentially usefull for many clinical
applications
 Stem cells can be collected from UCB,

Adipocytes and Peripheral Blood by Apheresis
 Stem cells can be Cryopreserved for use in
Cancers, CAD, Stroke, Diabetes, Burns, Spinal Cord
injury, Osteoarthritis, Regenerative medicine, etc.

Conclusions
 Adult
 stem cells can be obtained from
BM, Fetus, hUCB, Adipocytes and
Peripheral blood, It will not create any
ethical problems
 Adult stem cells from fetuses and hUCB
are the most PLASTIC
 Embryonic stem cells obtained from the
INNER CELL MASS for THERAPEUTIC
purposes are allowed in 38 countries (UK,
Sweden, Belgium, Netherland, China, India,
Korea, Taiwan, Singapore, Malaysia etc.)
 Embryonic stem cells for reproductive cloning

is not allowed in ALL COUNTRIES

5. Mesenchymal Stem Cells from BM,
Fetuses, hUCB, can be used as
Progenitor Neuronal Cells for
transplantation in Neurodegenerative
Diseases.
6. EPCs as well as MSC from BM, hUCB,
Adipocytes and peripheral blood can be
used for AMI
7. Stem Cell Research should become a
PRIORITY to be carried out in Indonesia
8. Academic Institutions, Business and
Government (ABG) must Cooperate Closely
to Stimulate RND for the Benefit of Society

Recent Advances in the Clinical Applications of Stem Cells

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