Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 74

5 Cell Sources for Cartilage Tissue Engineering
Chondrocytes are the primary cell type in cartilage and are an obvious cell source
to be explored for cartilage regeneration. Indeed, a clinical product approved by
the US Food and Drug Administration for articular cartilage repair, Carticel ,
involves autologous chondrocyte implantation. The surgical procedure associated
with the application of Carticel involves isolation of chondrocytes from a non-
load-bearing portion of cartilage, cell expansion, and subsequent implantation of
the autologous cells into the defect area. Recent studies have reported that 68% of
patients treated with Carticel had graft failure, delamination, or tissue hyper-
trophy [ 38 ]. One possible cause of these complications is the chondrocytes
themselves. In healthy tissue, chondrocytes are able to produce and breakdown the
ECM in a balanced manner. However, in damaged cartilage, chondrocytes are
generally unable to repair the tissue. The chondrocytes that are placed into
the defect site might not be integrating with the surrounding tissue and may
therefore hinder cartilage repair. Additionally, the limited quantity of chondrocytes
in cartilage requires in vitro culture to expand the cell number to clinically viable
levels. The simplest method to culture chondrocytes is to passage them in a
monolayer, but this may alter the morphology and dedifferentiate the chondrocytes
[ 39 ]. The cells tend to adopt a fibroblastic morphology and the levels of pheno-
typic expression markers such as aggrecan and type II collagen decrease with an
increase in the level of type I collagen, indicating a fibroblastic phenotype [ 39 ].
Transformation of the chondrocytes in this manner may result in fibrocartilage
tissue formation. Other studies have found that chondrocytes entrapped in a 3D
hydrogel such as alginate or agarose are able to retain a spherical morphology and
have shown their ability to redifferentiate [ 40 , 41 ]. A disadvantage of this approach
is that mature chondrocytes tend not to proliferate readily. Additionally,
3D constructs have diffusion limitations, with lower levels of nutrient and waste
exchange occurring in the center of the scaffold. Consequently, the size of the
construct is limited, which in the end affects how many cells can be entrapped
within the system. Further, it is difficult to achieve clinically relevant cell numbers
in 3D construct cultures as quickly as with monolayer cultures. Although under-
standing chondrocyte function is important to the development of approaches for
cartilage repair, major challenges are associated with the application of chon-
drocytes in strategies for cartilage regeneration. These limitations have led to the
investigation of alternative cell sources for promoting cartilage repair.
5.1 Stem/Progenitor Cell Sources
A variety of stem cell types can undergo chondrogenic differentiation and have
been investigated for application in cartilage tissue engineering. Stem cells are