Induced Pluripotent Stem (iPS) cells - as new tools for future

regenerative medicine and drug testing

Dr. Olga Ujhelly

BioTalentum Ltd., Hungary
Pluripotent stem cells have the capacity to become any cell
in the body

Differentiation
Somatic cells
Cardiac muscle
Skeletal muscle
Smooth muscle
Kidney tubule cell
Red blood cells
Lung cell
Thyroid cell
Pluripotent Pancreatic cell
stem cells Skin cell
Pigment cell
Neuron cell

Multiple differentiation potential = PLURIPOTENT

 Types of pluripotent stem cells
Embrionic stem cells - derived from blastocyst

Nuclear transfer-Embrionic stem cells - derived by somatic cell nuclear

Require embryos or eggs to create

New technology, developed by Shinya Yamanaka in 2006

Induced pluripotent stem cell

Derived from somatic cells without sacrificing embryos

Method of the Year 2009: iPS cells

 Generarion of induced pluripotent stem cells

In plutipotent stem cell a set of genes are active, which are required for maintaining
plripotency

In somatic cells most of these genes are inactive

Some genes required for

pluripotency:

Nanog
Oct4 Rex1
Zfp296
FoxD3
Sox2
ERAS Klf4 Fbxo
c-myc Dax1
 Generarion of induced pluripotent stem cells

In plutipotent stem cell a set of genes are active, which are required for maintaining
plripotency

In somatic cells most of these genes are inactive

Expression four of these genes in somatic cells induces pluripotency

Some genes required for

pluripotency:
Somatic cells Sox2 iPS cell
Nanog Oct4
Oct4 Rex1 Klf4
Zfp296 c-myc
FoxD3
Sox2
Klf4 Fbxo 2 weeks
ERAS
c-myc Dax1
Pluripotent stem cells can be generated from somatic cells

Differentiation
Somatic cells
Cardiac muscle
Skeletal muscle
Smooth muscle
Kidney tubule cell
Red blood cells
De-Differentiation Lung cell
Thyroid cell
Pluripotent Pancreatic cell
stem cells Skin cell
Pigment cell
Neuron cell

Multiple differentiation potential = PLURIPOTENT

 The characteristics of iPS cells are very similar to ES cells
• Morphology • In vitro differentiation
EB formation

• SSEA1 and alkaline phosphatase staining

• In vivo differentiation
Teratoma formation
In vivo pluripotency: chimeras
 iPS cells were generated from different species

2006 - Mouse
2007 - Human
2008 - Monkey
2009 - Rat
2009 - Pig
2009 - Dog
 Potential applications of iPS cells

Basic research
Studying signaling pathways involved in pluripotency
Studying early embryonic development
Studying development of different species
Generation models for human diseases

Conservation research
Generation iPS cells from endangered species

Pharmaceutical studies
Generation cell lines for drug testing

Therapy
Patient specific pluripotent stem cells, which can be differentiated to all the cell
types of the body

Cell replacement therapy for cardiac diseases, diabetes, parkinson disease etc.
Gene therapy - e.g. sickle cell anemia
Cell therapy - regenerative medicine

Somatic cells Sox2 c-myc iPS cell

Oct4 Klf4

De-differentiation

Differentiation
 Gene therapy

Somatic cells Sox2 c-myc iPS cell

Oct4 Klf4

De-differentiation

Hemoglobin gene
modification

Differentiation
Sickle cell anemia
Hemoglobin gene
mutation Hematopoietic Gene-modified iPS cell
stem cells