Biomedical Engineering Reference
In-Depth Information
microspheres could be significantly lower than that of trypsinized
cells. Cells cultured on macroporous PLGA microspheres could
survive much better than trypsinized adipose-derived stem cells
(ASCs)upontransplantation.Importantly,theimplantationofcells
culturedonmacroporousPLGAmicrospherescouldresultinmuch
more extensive tissue formation than the implantation of cells
cultured on plates and trypsinized.
Ex vivo
cell expansion and
transplantation using this system would improve the therapeu-
tic e
cacy of cells over the current methods used for tissue
engineering.
18.1 Introduction
Cell therapy and tissue engineering often require
in vitro
cell cul-
ture for cell expansion or lineage-specific differentiation of stem
cells. However, the current cell culture methods have several limi-
tations.Trypsinizationinterruptstheinteractionsbetweencultured
cellsandextracellularmatricessecretedfromtheculturedcells.This
may result in high apoptotic activity and reduced therapeutic e
-
cacyofthecellsupontransplantation.
1
Thelargesurfaceareaofthe
culture substrate is required to produce clinically relevant numbers
of transplantable cells, but the surface area of conventional, two-
dimensional(2D) culture plates constrains
ex vivo
cell expansion.
Biodegradablemacroporousmicrocarrierscombinedwiththree-
dimensional (3D), stirred suspension bioreactors could be an alter-
native culture system to avoid the limitations of current
ex vivo
cell
expansionmethodsforcelltherapyandtissueengineering.Amicro-
carrier is a microsphere with a diameter of a few hundred microm-
eters, provides a large surface area for cell attachment and growth,
and makes feasible 3D suspension cultures in a stirred suspension
bioreactor.
2
Microcarrier culture overcomes the limitation of cell
growth area in the 2D culture plate and thus would be suitable for
clinical-scale production of transplantable cells. Moreover, macrop-
orousmicrocarriersfurtherincreasethesurfaceareaforcellattach-
ment and growth and protect the cultured cells from shear stress
produced in a stirred bioreactor. A macroporous microcarrier that
is biodegradable and made of clinically approved biomaterials can
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