Biomedical Engineering Reference
In-Depth Information
found in periosteum-derived stem cells (PDSCs) [ 84 ]. However, further research
will be necessary to properly identify and locate chondrocyte precursors within the
bulk PDSCs. The exposure of PDSCs to growth factors such as TGF-b 1 , TGF-b 3 ,
FGF-2, and insulin-like growth factor (IGF)-1 significantly influences chondro-
genesis [ 85 - 87 ]. PDSCs and periosteum explants have been successfully cultured
in alginate, agarose, and atelocollagen gels, but the presence of growth factors is
necessary for successful neocartilage formation with these cells under these con-
ditions [ 87 , 88 ].
5.2 Fibroblasts
As an alternative to stem cells, fibroblasts are being investigated for cartilage
engineering. Almost every organ in the human body contains fibroblasts, which
originate from the mesoderm. An abundant source of fibroblasts can be isolated
from skin biopsies and can be used for potential autologous transplantation.
Fibroblasts have properties similar to those of MSCs, such as being able to adhere
to tissue culture plastic, being positive for CD73 and CD105, and being negative
for hematopoietic markers (e.g., CD14, CD34, CD45) [ 89 ]. Human dermal
fibroblasts (hDFs) are able to produce cartilage-like matrices containing compo-
nents such as chondroitin 4-sulfate and keratin sulfate when cultured on a colla-
gen-sponge-demineralized bone matrix composite [ 90 ]. Treating adult hDFs with
IGF-1 before culturing them on aggrecan led to production of type II collagen as
observed by immunohistochemical staining [ 91 ]. Additionally, exposing entrapped
neonatal hDFs in alginate beads to 5% oxygen with 100 ng/mL BMP-2 under
3 weeks of hydrostatic compression (1 Hz for 4 h/day) increased collagen pro-
duction and aggrecan gene expression compared with static culture conditions [ 92 ].
Dermis-isolated, aggrecan-sensitive cells, which are isolated by culturing dermal
fibroblasts in a monolayer on aggrecan, can be cultured as a micromass in an
agarose gel [ 93 ]. The dermis-isolated, aggrecan-sensitive cells have been shown to
produce a cartilage-like ECM. These results underscore the importance of
cell-ECM interactions. Additionally, cell-cell interactions have been shown to be
a significant parameter for fibroblasts to progress along a chondrogenic lineage.
Co-culturing hDFs with porcine articular chondrocytes on poly(lactic acid)/
poly(glycolic acid) as well as a micromass of hDFs with lactic acid has shown that
these cells are able to synthesize type II collagen [ 94 , 95 ]. Additionally, fibroblasts
reprogrammed to progress towards a chondrogenic lineage, such as BMP-7-
transduced fibroblasts cultured on collagen hydrogels, retrovirally SOX9 induced
fibroblasts, and fibroblasts induced by cartilage-derived morphogenetic protein 1,
have shown promising in vitro and in vivo results for the production of cartilage-
associated ECM proteins [ 96 - 98 ].
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