Biomedical Engineering Reference
In-Depth Information
broad differentiation ability into cells of all three germ layers [23, 24]. Despite these prominent
properties, ESCs are not applicable as cellular material for regenerative medicine tissue engi-
neering because of their immunologic incompatibility, the possibility of teratoma formation in
transplantations, and certain ethical issues [25]. Despite these issues, some attempts have been
made to overcome these problems so that stem cells can be used for human tissue regeneration.
For example, in 2012, human ESCs were used to regenerate the macula region of the retina in
phase I/II clinical trials [26]. The iPSCs are alternative ESC-like stem cells derived from somatic
cells [27, 28]. The main advantage of iPSCs is their production, which is not associated with the
sacrifice of a viable embryo. The discovery of iPSCs has created great promise for regenerative
medicine.
Mesenchymal stem cells are a subtype of adult stem cells (ASCs) defined as undifferenti-
ated cells, which are found throughout the body after birth [28]. They are nonhematopoietic
cells originally isolated by Fridenstein
et al
., and described as an adherent morphologically
fibroblastic cell population residing in marrow tissue. These authors stated that the most
important characteristics of MSCs are their capacity to produce small deposits of bone and
cartilage-like tissue in culture [39, 40]. Mesenchymal stem cells also have the capability to
give rise to neurons, keratinocytes, lung epithelial cells, liver cells, intestinal epithelial cells,
as well as kidney and spleen cells in addition to their well-recognized capacity to differen-
tiate into skeletal cell lineages [41, 42]. This ability of MSCs to produce cells other than
mesenchymal cell lineages is referred to as MSC plasticity [43].
The key feature of MSCs is their ability to form colonies that result from cellular activity,
referred to as colony-forming unit fibroblasts (CFU-F). The frequency of CFU-F in bone-
marrow samples is reported to be about 1 cell per 10
4
-10
5
mononuclear cells [40]. Nowadays,
MSCs are characterized by their ability for plastic adherence and capability of differentiation
into bone, cartilage, and adipose cell lineages. Although no distinct single surface antigen has
thus far been identified for MSCs, the Mesenchymal and Tissue Stem Cell Committee of the
International Society for Cellular Therapy has suggested certain markers that should be
examined on isolated cells. The expressions of CD73, CD105, CD90 and lack of expressions
of CD34 and CD45, CD14 or CD11b, CD19 or CD79a, along with the presence of plastic
adhesion property and potential to differentiate into three skeletal cell lineages qualifies the
cell under study to be designated as an MSC [44].
Mesenchymal stem cells lack ethical concerns; they are residents of multiple tissues and
can readily be differentiated along musculoskeletal cell lineages. Mesenchymal stem cells
possess immunomodulatory properties and injury-seeking capability. These features render
MSCs as preferable cellular candidates for cell-based treatment of tissue defects [45]. The
efficacy of MSCs in treating some human tissue defects is well established. Mesenchymal
stem cells have been used to cure osteogenesis imperfecta, regenerate bone-tissue defects,
reconstruct cardiac muscle after infarction, resurface articular cartilage, and restore hema-
topoiesis in patients receiving chemotherapy [46-50].
Cell-Nanomaterial Interaction
Nanomaterial topography remarkably affects cell attachment and proliferation. For
example, nanogratings have been reported to enhance cell adhesion, while nanopits and
nanoposts generally reduce cell attachment. Nanogratings, on the other hand, reduce
the rate of proliferation in comparison with planar substrates [51]. It has been reported that
the orientation of cells on biomaterial surfaces is dependent on the width of the groove.
Matsuzaka
et al
. have reported that rat MSCs follow the long axis in wide grooves and
prefer to bridge narrow grooves [52]. Cell differentiation can also be affected by nanoporous
