Biomedical Engineering Reference
In-Depth Information
Chapter 2
Pluripotent Stem Cells
Hossein Azizi
1,2,3
, Akbar Hajizadeh Moghaddam
2
, and Thomas Skutella
1
1
Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Medical Faculty,
University of Heidelberg, Heidelberg, Germany
2
Amol University of Special Modern Technologies, Amol, Iran
3
Department of Stem Cells and Developmental Biology at Cell Science Research Center,
Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Introduction
Pluripotent stem cells (PSCs) are undifferentiated cells that have the ability for proliferation,
self-renewal, and are able to differentiate into ectodermal, mesodermal, and ectodermal
cells of the embryonic germ layer (Figure 2.1) [1]. This potential of PSCs provides and
envisions an unlimited source of different cell types for regenerative medicine, tissue
replacement, drug screening, and functional genomics.
At present, several cell sources and methods for the generation of pluripotent stem cells
are available. One way is establishing embryonic stem cells (ESCs) after fertilization from
the inner cell mass of an embryo at the blastocyst stage [1, 2]. In the human this method is
associated with major ethical problems. Similarity to ESCs, embryonic germ cells (EGC)
also provide another source for pluripotent stem cells [3], but they possess a different
genomic methylation imprinting in comparison to ESCs [4]. Another approach is to gen-
erate these cells by transfection of pluripotency genes including Oct4, Sox2, Klf4, and c-Myc
into somatic cells that give rise to induced pluripotent stem cells (iPSCs) [5, 6]. This is a
simple and promising method for generation of patient specific stem cells; however, since
scientists so far mostly use retroviruses for transduction of the cells that integrate their
genome into the host cells, this approach might be very problematic in regenerative medi-
cine. Furthermore using oncogenes like c-Myc and Klf4 in the production of iPSCs leads to
further clinical roadblocks and controversial issues concerning the induction of cancer-
related genes during clinical application of these cells. Other nonviral approaches for the
generation of iPSCs are at the present stage either not widely reproducible (transfection of
proteins) or not very efficient (RNA) [7, 8].
Another promising natural nonmanipulating method for the establishment of PSCs
might be by germ cells such as spermatogonial stem cells (SSCs) [9-11]. Unipotent SSCs in
specific culture conditions could convert to a PSC state without the introduction of any
exogeneous pluripotency genes. Reports indicated that very small embryonic-like stem cells
isolated from an adult stem cells (ASCs) source [12] also showed pluripotency potential, but
