1. Agustina Setiawati, M.Sc., Apt
STEM CELL
Agustina Setiawati, M.Sc., Apt

2. DEFINITION What is a stem cell?
An undifferentiated precursor cell that can :
Proliferate (renewable source)
Differentiate-more than one cell type
Stem Cell = a cell which will reproduce itself and is also capable of giving rise to a more specialized cell.

3. Stem Cells Are a Breakthrough Technology
James Thomson, Ph.D in developmental biology, successfully cultured immortal, human embryonic stem cells in 1997.
Culmination of 17 years of research.
Science 282: (1998)
1999 Science Magazine “Breakthrough of the Year”.
Thomson on the cover of Time Magazine as one of the top scientists in the U.S.; numerous other news stories.
Two U.S. patents

5. Stem Cells can Both Differentiate and Continue Cycling (Self-Renewal)

6. 3 kinds of stem cells Based on their ability to differentiate:
Progenitor Stem Cell
Multipotent Stem Cell
Pluripotent Stem Cell

7. Progenitor Stem Cell
Those whose only can differentiate to single type cell

8. Multipotent Stem Cell
Stem cell which can differentiate to several type of cell constituting spesific tissue or organ
Ex: haemopoeitic stem cell
skin stem cell
neuron stem cell

10. Pluripotent Stem Cell
Are able to give rise of any kind type of cells, ex: embryonic stem cell

11. Which one can be derived from human body?

12. Models for stem cell
progression

13. Oops adult stem cells aren’t so flexible after all
Oops adult stem cells aren’t so flexible after all! Move to Embryonic Stem cells

14. True Embryonic Stem Cells Can Generate All Cell Types in the Body
Germ-line
Tissue-specific stem cells:

15. ES stem
Cells
Can make
Glia and
neurons

16. ES potential

17. Human ES cells

18. In vivo potential of human ES cells

20. How Embryonic Stem (ES) cells are derived

21. R C A primer on Human Embryonic Stem Cells Blastocyst -
from In Vitro Fertilization Clinic
“Blueprint” cells
Inner Cell Mass
(Stem Cells)
A Blastocyst is a hollow ball of cells with a small clump of stem cells inside R C

22. Human Embryonic Stem Cells
Blastocyst -
from In Vitro Fertilization Clinic
Stem Cells
“Blueprint” cells
A Blastocyst is a hollow ball of cells with a small clump of stem cells inside
Pipette
Stem Cells
“Blueprint”
cells
To remove the stem cells, the Blastocyst is opened and the stem cells removed with a pipette

23. Human Embryonic Stem Cells
Blastocyst -
from In Vitro Fertilization Clinic
Stem Cells
“Blueprint” cells
A Blastocyst is a hollow ball of cells with a small clump of stem cells inside
Pipette
“Blueprint”
cells
Stem Cells
Stem Cells
To remove the stem cells, the Blastocyst is broken open and the stem cells removed with a pipette(an ultra thin glass tube)
The stem cells are placed in a
dish and are fed and cared for
(each blastocyst =
1 stem cell line)
Pipette
Petri Dish

24. Stem Cells are Sometimes Purified Using Specific Cell Surface Markers

25. Pancreatic Islet Muscle cell Neuron
Growth factors
Chemical cues
Petri Dish
Stem Cells
Pancreatic
Islet
Muscle
cell
Neuron
Different chemicals / molecules are added to the stem cells to make them become specific types of cells.

26. Can bone marrow stem cells also make cardiac muscle
Can bone marrow stem cells also make cardiac muscle? Stem cell medicine meets basic science story

28. New mouse data, does it matter if we don’t know what the cells
Are doing? What are they doing? (vessels, growth factors)

29. What can mislead us with adult stem cell studies?
Make sure single cell, clonal origin for transplantability of proliferation and differentiation
Not always test for self renewal properties
Concern with cell fusion

30. How can stem cells be used to treat diseases?
Stem cells as “REPLACEMENT PARTS”:
A wide range of diseases (heart disease, Parkinson’s, Alzheimer’s, diabetes, motor neuron disease, etc.)
Stem cells were directed to the appropriate place in the body and become the appropriate cell type.

31. How can stem cells be used to treat diseases?
2) Developing drug therapies:
It is possible to make stem cells that are genetically identical to those of a patient with a disease.
The stem cells can be made to generate the cell type that is defective in that disease.
By studying these cells, we can gain insight into what goes wrong at the molecular level in the disease.
We can also use these cells to test drugs that might block the progression of the disease

32. The vision for UCI’s Stem Cell Center: Stem cell therapies for neurological disorders
Brain and spinal cord injury.
Stroke.
Neurodegenerative diseases
Parkinson’s Disease
Huntington’s Disease
Alzheimer’s Disease
Multiple Sclerosis
Lou Gerhig’s Disease (ALS)
Reeve-Irvine Research Center

33. Neurodegenerative diseases
Neurological disorders involve the loss of particular cell types in the nervous system
Brain and spinal cord injury and stroke (loss of nerve cells and myelin-forming oligodendrocytes).
Neurodegenerative diseases
Parkinson’s Disease (loss of dopamine-containing nerve cells in the brainstem).
Huntington’s Disease (loss of nerve cells in the striatum).
Alzheimer’s Disease (loss of nerve cells in the cerebral cortex).
Multiple Sclerosis (loss of myelin-forming oligodendrocytes).
Lou Gerhig’s Disease-ALS (loss of motor neurons from the spinal cord).
The vision: To use embryonic stem cells to restore the cells that are lost as a result of injury or neurodegenerative diseases.
Reeve-Irvine Research Center

34. Approaches to Stem Cell Therapies For Neurological Disease
Transplantation of neural stem cells
Donor: fetal brain
Advantages
Disadvantages

35. Risk of graft vs. host disease; Immunosuppression needed
Approaches to Stem Cell Therapies For Neurological Disease
Transplantation of ES cell-derived neural stem cells
Donor: blastocyst
Advantages
Disadvantages
Material comes from IVF clinics;
access to aborted fetal tissue not
required
Risk of graft vs. host disease; Immunosuppression needed

36. “somatic cell nuclear transfer” aka “therapeutic cloning”
Approaches to Stem Cell Therapies For Neurological Disease
Transplantation of ES cell-derived neural stem cells
Donor: nuclear transfer
“somatic cell nuclear transfer” aka
“therapeutic cloning”
Advantages
Disadvantages
-economics
Pending legislation to criminalize procedure

37. Approaches to Stem Cell Therapies For Neurological Disease
Transplantation of adult brain cells
Donor: adult brain
Advantages
Disadvantages

38. Approaches to Stem Cell Therapies For Neurological Disease
In vivo mobilization of endogenous brain stem cells with growth factors
Advantages
Disadvantages
Not all brain regions may respond to the factors

39. Can it develop to be a cancer?

40. Cancer stem cell theory
New cancer model:
1) Cancer arise from cells termed cancer stem cells that have properties of normal stem cells, particularly self-renewal and multipotentiality (a minority) of tumor cells.
2) Unregulated cell growth is due to a disruption in the regulatory mechanism in stem cell renewal.
3) Cancer is a stem cell disorder and not a simple mechanism whereby cell proliferation is disrupted.

41. Cancer stem cell theory
These CSCs cells persist in cancer as a distinct population that likely causes relapses and metastasis.
This theory explains why are many cancers so difficult to treat.

42. Cancer stem cell theory
Why stem cells?
Only stem cells have the ability to self renew and neoplasia is essentially dysregulated self renewal
Stem cells are long-lived cells which can acquire the necessary number of sequential mutations to convert a normal cell into a malignant one.

43. Are we targeting the right cells?
Conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate a new one.
A population of CSCs, which gave rise to it, remains untouched and may cause a relapse of the disease.
Development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease, where little progress has been made in recent years.

44. Cancer vs Cancer Stem cell

45. Strategy to kill CSC

46. Any question?

47. TERIMA KASIH