Biomedical Engineering Reference
In-Depth Information
kpa), resembling muscle, they differentiate into myoblasts; on stiff substrates
(25-40 kpa), resembling osteoid, MSC differentiate into osteoblasts. it
should be noted that if this 'physical' commitment is prolonged for a few
weeks, the differentiation to a lineage is not reversed by the addition of
soluble factors specific for another lineage, consistent with the relative
insensitivity of differentiated cells to elasticity. this underlines the role
of the microenvironment, and specifically of the mechanical properties, in
determining the fate of undifferentiated cells and may be suggested as an
additional mechanism for MSC homing (Fig. 3.4).
Multipotent MSC are attractive for tissue engineering approaches. in fact
(1) they are a population of adult undifferentiated cells that can be obtained
without previous mobilization; (2) they can be easily isolated from the BM
through simple mechanical disruption; (3) they are able to escape recognition
by immune cells and exhibit immunosuppressive effects; and (4) under optimal
conditions, they can undergo 25-40 passages
in vitro
, demonstrating a good
capacity for self replication.
three different modes of delivering MSC in scaffolds at the implant site
are currently being investigated: MSC loaded into scaffolds
in vitro
and,
after a short incubation, implantation of the cell-loaded scaffold; cell-scaffold
composite incubated in differentiation medium to stimulate MSC progression
into a specific lineage; and implantation of scaffold with specific sites for
cell anchorage or factors recruiting cells (chemotaxis). these approaches
have been used in animal models but rarely in humans.
MSC
Growthfactors,pO
2
100kPa
1kPa
10kPa
Matrixelasticity
Muscle
Bone
Neuronal
3.4
ThedifferentiationofMSCstocelllineagesisinluencedbythe
complianceofthesurroundingextracellularmatrix,too,whichgives
amechanicalsignaltothecells.AsdescribedbyEngler
et al
.,
40
asoftsubstrate(1kPa)mayinduceMSCstoaneuronaltype;an
intermediate(10kPa)tomyoblasticcell,andarigidone(100kPa)
turnsMSCstoosteoblasts.
