Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

EMBRYONIC AND ADULT STEM CELLS IN REGENERATIVE MEDICINE I.

István SzatmáriMolecular Therapies- Lecture 10

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

The aim of this lecture to define and characterize the embryonic and adult stem cells. This lecture also covers the necessary basic concepts of cell reprogramming and lineage conversion.

Table of contents

10.1. Embryonic stem (ES) cellsDefinition of stem cellsClassification of stem cellsGeneration of human ES cellsGeneration of transgenic and knock out animals

10.2. Somatic cell reprogramming into pluripotent stem cells3 ways to reprogram somatic cells into pluripotent cellsAnimal cloningGene delivery methods for iPS reprogrammingLineage specific reprogramming by transcription factorsThe promise of ES/iPS cell research

10.3 Adult stem cellsDefinition of adult (tissue specific) stem cellsExample for an adult stem cell

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The most important characteristics of embryonic stem (ES) cells:

Self-renewal: Unlimited proliferation capacity without differentiation (immortality).

Pluripotency: they are able to develop into all types of somatic cells that make up the body.

ES specific markers:

- Transcription factors: Oct4, Nanog, Sox2- Alkaline phosphatase- SSEA1 (mouse ES cells)- SSEA3/4 (human ES cells)- Telomerase activity

Factors for maintaining the pluripotent state:

- LIF, BMP4 (mouse ES cells)- bFGF, activin (human ES cells)

Murine embryonic stem cell culture.

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advantage:

Oocytes or embryos do not need for iPS cell generation.

There are no ethical issues (disruption of human embryos).

iPS cells can be obtained from various somatic cells.

iPS cells can be generated from patients.

Disadvantage:

iPS cells contain transgenes (reprogramming factors), these ectopic genes might interfere cell differentiation and over-activation of these genes (e.g. c-myc) can promote tumorigenesis.

iPS cells are very similar to ES cells but several recent reports suggested that iPS cells have an impaired developmental potential. For example, getting tetraploid complementation with adult tissue derive iPS cells has not been successful.

iPS cells are often partially reprogrammed (e.g. these cells retain the DNA methylation pattern of the original somatic cells).

ES versus iPS cells TÁMOP-4.1.2-08/1/A-2009-0011

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adult (tissue specific) stem cells: Adult stem cells are multipotent (or unipotent) cells, found throughout the body after embryonic development. These cells have the capacity to self-renew and to regenerate tissues long-term, in addition, they only differentiate to cell types within their lineage.

Examples:

Hematopoietic stem cells (blood stem cells)

Mesenchymal stem cells

Muscle stem cells (satellite cells)

Intestinal stem cells

Neural stem cells

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