Biomedical Engineering Reference
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tension within the actin cytoskeleton, simultaneously being negative regulators of
both adipogenic and chondrogenic differentiation [ 204 ]. Low oxygen throughout
the cultivation time of mesenchymal progenitor cells elevates culture markers for
osteogenesis, including alkaline phosphatase activity, calcium content, and von
Kossa staining [ 205 ]. Local Ca 2+ concentration influences cell morphology through
the cell-cell or cell-matrix interactions of osteoblasts, thus affecting osteogenic
differentiation while not influencing proliferation [ 206 ]. Calcium and purine
derivates can also directly influence the lineage commitment of MSCs to the
adipo- or osteogenic lineages via P receptors. Several specific P2 receptors are
involved in this process. P2Y5 and P2Y14 influence proliferation of MSCs, and
P2X6 up- or down-regulation is plays a key role in the lineage commitment of SCs
between the adipogenic or osteogenic lineages, respectively [ 187 ].
Another unsolved problem of large bone defects is the necessity of angiogen-
esis. MSCs have been shown to differentiate in vitro not only into the osteogenic
lineages and others, but also into endothelial cells, which are the fundamental cells
for angiogenesis. Although the sprouting of endothelial cells to form new vessels
has already been demonstrated [ 207 ], and although the size of the interconnecting
pores needed within the scaffold for the vessel is known as well as major inducing
factors such as vascular endothelial growth factor (VEGF), this final step towards
an artificial scaffold for large bone defects needs more basic research efforts before
a breakthrough achievement permits clinical trials with such an approach. Until
now the sprouting new vessels are too small and the inducing factors have severe
side effects such as an increase in carcinogenesis.
5.2 MSCs for Dental Tissues
Several different problems must be faced in dentistry and efforts are being made to
create new solutions for old problems on the basis of SCs used for regenerative
approaches. One major problem is the tooth decay formerly known as dental
caries. Here replacement of the enamel with or without dentine would be bene-
ficial. Even the re-growth of full teeth is already being considered and researched.
The second problem is periodontitis, which represents a major health problem
worldwide. Periodontal defects primarily evolve as a consequence of inflammation
and do not heal spontaneously. Root cementum is the major hard tissue which
must be considered if this problem is to be addressed. Last but not least, tooth loss
due to tooth decay or periodontitis creates a need for bone reconstruction and
implant stabilization. Taken together, dental materials contain all calcified tissues
of the body: enamel and dentine within the teeth and root cementum and alveolar
bone in the periodontium. For an overview of tooth organogenesis and regenera-
tion see Thesleff and Tummers [ 208 ].
Considerable efforts have been made to identify SCs in dental tissues
(e.g., SCAPs, see ''MSCs and Ectomesenchymal SCs'' and [ 82 ]. However, the
availability of dental SCs is limited as it is restricted to specific time points. SCs
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