Recent Advances in the Clinical Applications of Stem Cells

National
Insitute of
Health
Guidelines for
Stem Cell
Research
Recent Advances in the
Clinical Applications of
Stem Cells
Dr. Boenjamin Setiawan, Ph.D.
Chairman Stem Cell and Cancer
Institute
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Countries colored in brown represent about 3.5 billion people, more
more
than half the world's population. All have a permissive or flexible
flexible
policy on human embryonic stem cell research and all have banned
@ 2006 Terese
Winslow
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dr.Boenjamin Setiawan,Ph.D.
World Stem Cell Research Centers
human reproductive cloning.
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dr.Boenjamin Setiawan,Ph.D.
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dr.Boenjamin Setiawan,Ph.D.
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Mengapa ABG penting??
Akademi adalah sumber SDM terdidik dan
sumber IPTEK
Selama dana pemerintah utk R&D kecil maka
2.
sebaiknya Fokus pd IPTEK Teraplikasi
Bisnis adalah tempat untuk mengkonversi
3.
IPTEK menjadi produk praktis yang bermanfaat
untuk masyarakat
Government adalah KATALISATOR untuk
4.
menciptakan peraturan yang kondusif untuk
INOVASI melalui R&D
ABG harus membentuk kerjasama yang
5.
terintegrasi secara “SEAMLESS”
SEAMLESS”
Budaya saling mempersulit harus diubah
6.
menjadi BUDAYA SALING MEMBANTU=GOTONG
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ROYONG
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1.
5050-100 Trillion Cells form the
Building Block of the Human Body
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dr.Boenjamin Setiawan,Ph.D.
The Human Body
z Consist
of 12 Organ Systems
z Consist of 220 types of Tissues
z Consist of 5050-100 trillion cells
z Consist of 100 billion neurons
z Consist of 46 chromosomes (22 pairs and
x and y chromosomes)
z Consist of 30.000 genes
z Consist of 3,2 billion base pairs
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DNA, the genetic code is principally
found in the Nucleus of each cell
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Consequently DNA is double stranded that
wound round each other in a double helix
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dr.Boenjamin Setiawan,Ph.D.
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dr.Boenjamin Setiawan,Ph.D.
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
dr.Boenjamin
Setiawan,Ph.D.
self-regenerate/self-renew
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Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676
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dr.Boenjamin Setiawan,Ph.D.
dr.Boenjamin Setiawan,Ph.D.
Stem Cells
are taken
from the
Inner Cell
Mass at the
blastocyst
stage and
cultured in
a Petri disk
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Adult Stem Cells: Bone Marrow
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Plasticity of Adult Stem Cells
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Therapeutic cloning
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dr.Boenjamin Setiawan,Ph.D.
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dr.Boenjamin Setiawan,Ph.D.
Stem Cell Banking
1.
2.
3.
4.
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.
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The cardiovascular
z
Target Diseases for Stem Cell Therapy
Blood Diseases
Bone marrow transplants (BMT) are a well known clinical
application of hematopoietic stem cell (HSC) therapy
z HSCs can regenerate all of the different cell types in blood
z 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
z
z
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1.
2.
3.
4.
circulatory system’
system’s main
role is to transport
nutrients and oxygen to the
5050-100 trillion cells that
makes up our body and
remove the waste material
from the body.
The most prevalent disease
that affects the CVS is:
Atherosclerosis
Hypertension
Acute myocardial infarction
Stroke
dr.Boenjamin Setiawan,Ph.D.
Target Diseases for Stem Cell Therapy
Heart Disease
ES cells can be induced to form cardiac muscle cells that
actually beat in culture
z When transplanted into damaged hearts, these cells can
form gap junctions and contract in unison with
surrounding cells
z HSCs can also be grafted into damaged heart muscle and,
in this new environment, are reprogrammed to produce
heart cells instead of blood cells
z
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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
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Pediatric Research 59:26R-32R (2006)
© 2006 International Pediatric Research Foundation, Figure
Inc. 1. EPCs are bone marrowDOI: 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 proangiogenic monocytes (blue) to
locate behind the endothelial
wall and support the stability and
viability of the local endothelium
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by paracrine mechanisms
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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
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z
1.
2.
3.
4.
5.
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To
Prevent
AtheroAtherosclerosis
Control
cholestero
l level
Control
Hypertens
ion
Exercise
Diet
No
smoking
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Differentiation of embryonic
cells into the cardiac lineage
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Physiol. Rev. 85: 1373-1416, 2005; doi:10.1152/physr “Cardiac Stem Cells and
Mechanisms of Myocardial Regeneration”
Therapeutic Potential of EPC in AMI
z
Figure 2. Therapeutic
potential of EPCs.
EPCs.
Intracoronary infusion of
EPCs in patients with AMI
may have the potential to
restore myocardial
function to the damaged
area.
area.
EPC transplantation
increases left ventricular
ejection fraction (LVEF),
coronary blood flow
reserve, and myocardial
viability and decreases
left ventricular endendsystolic volume
dr.Boenjamin Setiawan,Ph.D.
(LVESV).66
(LVESV).66
z
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z 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.
z The most prevalent diseases
that affect the CNS is Stroke,
Parkinson’
Parkinson’s disease,
Alzheimer’
Alzheimer’s disease, ALS
and Autism
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Proposed Mechanism for Stem
Cells in Neurodegenerative
Diseases
z Implanted
stem cells migrated &
integrated extensively throughout the
brain
z Some of the transplanted cells replaced
damaged nerve cells and transmitted
nerve impulsesÆ
impulsesÆ integrate electrically and
functionally into a diseased brain
z stem cells employ multiple mechanisms Æ
not just cell replacement - which
collaborate to benefit diseaseLee et al, Nature 2007
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Brain Cell Transplantation
z
z
z
z
z
z
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
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Ischemic
Stroke
Target Diseases for Stem Cell Therapy
Brain and Spinal Cord
Injury
Neural stem cells can be
isolated from adult brains or
generated from ES cells in
culture
z HSCs can also be
transplanted into the brain
where they are
reprogrammed to generate
neurons and glial cells
z Potential applications include
Parkinson’
Parkinson’s disease, ALS,
Huntington’
Huntington’s disease, stroke,
Alzheimer’
Alzheimer’s disease, paralysis
z Animal and early human
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trials
z
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z 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
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Published in 2005 (Cytotherapy)
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Parkinson’
Parkinson’s Disease :
Degeneration of brain cells
z
Cells in the
z
Loss of the
chemical
substantia nigra
dopamine
z
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No clear reason
why
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Osteoarthritis and Autoimmune
Diseases
z Mesenchymal
stem cells are
used to be
inserted into the
synovial cavity
where they
transdifferentiate
into chondroblasts
and form new
cartilage
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Osteoarthritis of the Knee Joint
z Mesenchymal
stem
cells are implanted
into a
biodegradable
scaffold and
inserted into the
synovial cavity
where they will
transdifferentiate
into new cartilage
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Target Diseases for Stem Cell Therapy
Type 1 Diabetes
Patients lack pancreatic
beta cells and cannot
produce insulin
z InsulinInsulin-producing
structures similar to
pancreatic islets have been
generated from mouse ES
cells in culture
z It may also be possible to
isolate pancreatic stem
cells from adult tissue
z Early stage of development
z
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Conclusions
Stem Cell Banking
1.
2.
3.
4.
5.
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.
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5. Mesenchymal Stem Cells from BM,
Fetuses, hUCB,
hUCB, can be used as
Progenitor Neuronal Cells for
transplantation in Neurodegenerative
Diseases.
6. EPCs as well as MSC from BM, hUCB,
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
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1.
2.
3.
4.
Adult stem cells can be obtained from
BM, Fetus, hUCB,
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
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