Biomedical Engineering Reference
In-Depth Information
the presence of bone precursors in the circulating blood is contentious.
isolation of mesenchymal precursor cells has been obtained with or without
prior growth factor mobilization, but the yield is very low and dependent on
the isolation method.
33
the number of such precursors may be underestimated
owing to the technique of isolation through plastic adherence. interestingly,
their frequency increases after bone fractures, acute burns and myocardial
infarction.
34, 35
as previously mentioned, subendothelial pericytes, which
provide mechanical support, stability, and contractility to small and large
vessels, are claimed to be MSC precursors, as they originate osteoblasts,
chondroblasts and adipocytes.
36
MSC can also be grown from adult human liver and heart. Similarly to adult
BM derived cells, a population of multipotent, clonogenic, telomerase-positive
cells, able to differentiate into cell types morphologically and functionally
corresponding to derivatives of the three germ layers, was produced in
culture.
37
this population is likely to correspond to the 'multipotent adult
progenitor cells' described below.
despite a body of literature describing the putative adult MSC, evidence that
multipotent MSC actually exist
in vivo
is still lacking. a potential equivalent
of ESC has been identified within the MSC adult heterogeneous population
and termed multipotent adult progenitor cells (MapC). MapC show some
features of ESC, including differentiation potential for multilineages, extensive
proliferation and, when injected into an early blastocyst, contribution to most
somatic cell types.
38
in summary, these cells, similar to ESC, fully gratify the
stem cell definition, but in contrast to ESC, can be selected from autologous
BM and used undifferentiated without the risk of teratoma formation, or,
after genetic manipulation, in local and systemic therapies.
it is hard to develop a consensus opinion about MSC plasticity, since the
differences in experimental protocols result in different MSC populations
being isolated and assayed. MSC can repair injured tissue by differentiating
into the phenotype of damaged cells, by releasing cytokines and growth
factors and by undergoing cell fusion. the ability of MSC to differentiate into
committed cells, that is, adipocytes or chondrocytes, to be followed by their
'regression' to an intermediate step (de-differentiation) and progression along
the osteoblastic lineage, as well as an epithelial-to-mesenchymal transition
process, termed 'transdifferentiation', have been referred to as evidences
of their
in vivo
plasticity. however, according to some authors, cell fusion,
instead of transdifferentiation or de-differentiation, is the process underlining
the change of MSC from a phenotype to another and the plasticity of MSC
might be simply related to population heterogeneity.
39
the matrix compliance may initially guide MSC into a development
lineage, even if is not sufficient to complete terminal differentiation.
40
on
soft substrates (0.1-1 kpa) mimicking the compliance of brain tissue, MSC
show a neuronal phenotype; on substrates of intermediate stiffness (8-17
