Agustina Setiawati, M.Sc., Apt

STEM CELL

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.

DEFINITION

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: 1145-1147 (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

Stem Cells can Both Differentiate and

Continue Cycling (Self-Renewal)

3 kinds of stem cellsBased on their ability to differentiate:

1. Progenitor Stem Cell2. Multipotent Stem Cell3. Pluripotent Stem Cell

Progenitor Stem Cell Those whose only can differentiate to

single type cell

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

Pluripotent Stem Cell Are able to give rise of any kind type of

cells, ex: embryonic stem cell

Which one can be derived from human body?

Models for stem cellprogression

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

True Embryonic Stem Cells Can Generate All Cell Types in the Body

Tissue-specific stem cells:

Germ-line

ES stemCellsCan makeGlia andneurons

ES potential

Human ES cells

In vivo potential of human ES cells

How Embryonic Stem (ES) cells are derived

Blastocyst -from In Vitro Fertilization Clinic

Inner Cell Mass(Stem Cells)

“Blueprint” cells

A primer on Human Embryonic Stem Cells

A Blastocyst is a hollow ball of cells with a small clump of stem cells inside

R RC

“Blueprint” cells

Human Embryonic Stem Cells

Pipette

Stem Cells

To remove the stem cells, the Blastocyst is opened and the stem cells removed with a pipette

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

Pipette

Stem Cells

Petri Dish

Human Embryonic 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)

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

Stem Cells

“Blueprint” cells

Stem Cells are Sometimes Purified Using Specific Cell Surface Markers

NeuronMuscle

cell

Pancreatic Islet

Petri DishStem Cells

Different chemicals / molecules are added to the stem cells to make them become specific types of cells.

Growth factors Chemical cues

Can bone marrow stem cells also make cardiac muscle?

Stem cell medicine meets basic science story

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

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

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.

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

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

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

Approaches to Stem Cell Therapies For Neurological Disease1. Transplantation of neural stem cells

Donor: fetal brain

Advantages Disadvantages

• Risk of graft vs. host disease; Immunosuppression needed

Material comes from IVF clinics;access to aborted fetal tissue notrequired

Advantages Disadvantages

Approaches to Stem Cell Therapies For Neurological Disease

2. Transplantation of ES cell-derived neural stem cells

3. Donor: blastocyst

-economicsPending legislation to criminalize procedure

“somatic cell nuclear transfer” aka“therapeutic cloning”

Advantages Disadvantages

Approaches to Stem Cell Therapies For Neurological Disease

3. Transplantation of ES cell-derived neural stem cells

Donor: nuclear transfer

Approaches to Stem Cell Therapies For Neurological Disease

4. Transplantation of adult brain cells

Donor: adult brain

Advantages Disadvantages

• Not all brain regions may respond to the factors

Approaches to Stem Cell Therapies For Neurological Disease

5. In vivo mobilization of endogenous brain stem cells with growth factors

Advantages Disadvantages

Can it develop to be a cancer?

Cancer stem cell theoryNew 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.

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.

Cancer stem cell theoryWhy 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.

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.

Cancer vs Cancer Stem cell

Strategy to kill CSC

Any question?

TERIMA KASIH