Biomedical Engineering Reference
In-Depth Information
should aim at harnessing the full potential of implanted MSC to enhance
their in situ survival not only to improve their engraftment and transdif-
ferentiation, but rather to enhance their autocrine and paracrine effects to
trigger host endogenous regeneration cascades [67] (Figure 6.8).
Using state-of-the-art bioengineered materials will allow enhanced
control of cells and presentation of the MSC secretome after transplan-
tation. MSC can be primed to modify their secretome by internalizing
1-2 micron-sized biodegradable particles containing differentiation par-
ticles [77]. Enhancing MSC homing to the injury site to enhance their auto-
crine and paracrine effects has also been approached by engineering the
surface of MSC using adhesion ligands to enhance cell rolling which is
a crucial step in cell homing [78]. Furthermore, delivering the cytokines
on their own by a controlled release device may partially mimic cellular
effects or alternatively enhance endogenous cell ability to respond to injury
signals and direct tissue repair in the absence of transplanted cells [71].
6.4.2 Infl ammation, Angiogenesis and Tissue Repair
It is the injury microenvironment that dictates how the healing process
will proceed. Particularly the infl ammatory phase of the wound healing
cascade that further modulates angiogenesis and tissue formation and
that unduly affects the performance of transplanted MSC.
Endogenous
regeneration
Steady state turnover
Mobilization
Quiescent
niche
BONE
( a )
Outside
stem cells
Injury signals
Quiescent niche
Cell delivery
Replenish
niche
Mobilization
Stem cells
Progenitor cells
DEFECT
Tissue-forming cells
Exogenous
regeneration
( b )
Figure 6.8 Schematic illustration of tissue regeneration via (a) endogenous
regenerative approaches, and (b) exogenous cell delivery technologies. Reprinted
with permission from [2].
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