Biomedical Engineering Reference
In-Depth Information
2. Stem cells
Stem cells are undifferentiated cells, with endless self-renewal sustained proliferation
in
vitro
and multilineage differentiation capacity [3]. This
in vitro
multilineage differentia‐
tion capacity has targeted these cells with extreme importance for use in tissue and cell-
based therapies.
The first stem cell appearance is in the early zygotic cells, which are totipotent and give rise
to the blastocyst. They are capable to differentiate into all cell and tissue types. With differ‐
entiation, cells become less capable of self-renewal and differentiation in other cell type be‐
comes more limited [1]. Stem cells can be loosely classified into 3 broad categories based on
their growth behavior and isolation time during ontogenesis: embryonic, fetal and adult.
Embryonic stem cells (ESCs) were first observed in a pre-implantation embryo by Bongso
and colleagues in 1994 [4]. Since then, many cell lines and a multiplicity of tissues have been
successfully derived from ESCs and tested in several animal disease models [5-7]. Neverthe‐
less, post-transplantation immune-rejection has been a major problem. Many studies are be‐
ing conducted to avoid this major issue. This could be resolved by personalizing tissues
through somatic nuclear transfer (NT) or induced pluripotent stem cells (iPSC) techniques
[8], but the teratoma development in animals is still a concern and a serious problem [9]. In
order to overcome the limitations placed by ESCs and iPSCs, a variety of adult stem cell
populations have been recently isolated and characterized for their potential clinical use.
While still multipotent, adult stem cells have long been considered restricted, giving rise on‐
ly to progeny of their resident tissues [9].
In vivo,
adult stem cells exist in a quiescent state,
located in almost all tissues, until mediators activate them to restore and repair injured tis‐
sues. These cells are surrounded by mature cells that have reached the end line in terms of
differentiation and proliferation [10]. Stem cell research focuses on the development of cell
and tissue differentiation, so as characterization techniques, for tissue and cell identification
with marker patterns. Such protocols are essential for regenerative therapies [11].
2.1. Mesenchymal stem cells
The development of cell-based therapies for cartilage [12] and skin [13] reconstruction
marks the beginning of a new age in tissue regeneration. Mesenchymal stem cells (MSCs)
have become one of the most interesting targets for tissue regeneration due to their high
plasticity, proliferative and differentiation capacity together with their attractive immuno‐
suppressive properties. MSCs present low immunogenicity and high immunosuppressive
properties due to a decreased or even absence of Human Leucocyte Antigen (HLA) class II
expression [14]. Research in this field has brought exciting promises in many disorders and
therefore in tissue regeneration. Currently the differentiation potential of MSCs in multiline‐
age end-stage cells is already proven, and their potential for treatment of cardiovascular
[15], neurological [16], musculoskeletal [17, 18], and cutaneous [19] diseases is now well es‐
tablished. Fibroblast colony-forming units or marrow stromal cells, currently named MSCs,
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