Biomedical Engineering Reference
In-Depth Information
16.4.1 Origin of mesenchymal stem cells
MSCs are stem cells derived from somatic tissues which can be differentiated into mesenchymal
lineages such as bone, cartilage, fat, and skin. In addition, MSCs are present in many connective
tissues and blood at low concentrations serving as a sort of internal repair system. MSCs are distin-
guished from other cell types by two important characteristics. First, they are unspecialized cells
able to renew themselves through cell division, sometimes after long periods of inactivity. Second,
under certain physiologic or experimental conditions, they can be induced to become tissue- or
organ-specific cells with special functions. MSCs have high proliferative and multipotent capacity
leading to differentiated cells under the guidance of various cues or niches. MSCs are convention-
ally defined as adherent, non-hematopoietic cells expressing markers such as CD13, CD29, CD44,
CD54, CD73, CD90, CD105, and CD166, and being negative for CD14, CD34, and CD45 [28,29] .
While originally identified in the bone marrow [30] MSCs have been extracted from numerous
tissues including adipose [31,32] , heart [33] , dental pulp [34] , peripheral blood [35] , and cord
blood [36] . One of the major properties of MSCs is their ability to differentiate into various cells
like adipocytes [37] , chondrocytes [31] , osteoblasts [38] , neurons [39,40] , muscles [40,41] , and
hepatocytes [42] in vitro after treatment with induction agents.
16.4.2 Migration, adhesion, and proliferation
The integration of implant with neighboring bone and gingival tissue depends on successful cross
talk between old tissue and implant surface. The challenge in dental implant research is the capabil-
ity of the surface to guide cells' colonization and differentiation. Cell migration, adhesion, and pro-
liferation on implant surfaces are a prerequisite to initiate the tissue regeneration ( Figure 16.5 ).
Authors have shown that some factors present in tissues and secreted during the inflammatory
phase are able to attract MSCs to the injured site [43,44] . MSCs migration and proliferation were
stimulated in vitro by many growth factors including Platelet-derived growth factor (PDGF)
[45,46] , Epidermal growth factor (EGF) [46,47] , Vascular endothelial growth factor (VEGF) [48] ,
Transforming growth factor (TGF-
) [45,49] , Bone morphogenetic protein-2 (BMP-2) and BMP-4
[45,48] . These factors are certainly released in the injured sites by cells involved in tissue healing.
Furthermore, plasma clot serves as storage to fibrin molecules and release system for a variety of
bioactive factors including growth factors that attract and differentiate MSCs into specific lineages
[50
β
52] . The platelet factors are well known to stimulate the proliferation of MSCs [53] . The for-
mation of a clot matrix with a potent chemo-attractive factor like PDGF, EGF, or fibrin may further
enhance MSCs numbers and periimplant tissue healing surface. Moreover, the plasma clot in con-
tact with implant surface represents a three-dimensional microporous structure that allows diffusion
of regulatory factors [54,55] and is involved in the migration, proliferation, and differentiation of
MSCs. After MSCs recruitment in the injured site, cells adhere on the local extracellular matrix as
well as on the implant surface beginning an extensive proliferation in order to build up new tissue.
Again, surface modifications of implants in the nanometer range condition the biological responses.
16.4.3 Differentiation
In the microenvironment, MSCs are stimulated by some specific factors to differentiate into the
adequate cell line. Under the influence of these factors, MSCs switch to osteoblastic cells in contact
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