1. Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. EMBRYONIC AND ADULT STEM CELLS IN REGENERATIVE MEDICINE I. István Szatmári Molecular Therapies- Lecture 10 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

3. 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) cells Definition of stem cells Classification of stem cells Generation of human ES cells Generation of transgenic and knock out animals 10.2. Somatic cell reprogramming into pluripotent stem cells 3 ways to reprogram somatic cells into pluripotent cells Animal cloning Gene delivery methods for iPS reprogramming Lineage specific reprogramming by transcription factors The promise of ES/iPS cell research 10.3 Adult stem cells Definition of adult (tissue specific) stem cells Example for an adult stem cell TÁMOP-4.1.2-08/1/A-2009-0011

6. 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. TÁMOP-4.1.2-08/1/A-2009-0011

13. 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

16. 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 TÁMOP-4.1.2-08/1/A-2009-0011