Background: An entire articular condyle engineered from stem cells
may provide an alternative therapeutic approach to total joint replacement.
This study describes our continuing effort to optimize the chondrogenic and
osteogenic differentiation from mesenchymal stem cells toward engineering
articular condyles in vivo.
Methods: Primary rat bone-marrow mesenchymal stem cells were induced
to differentiate into chondrogenic and osteogenic lineages in vitro and were
suspended in polyethylene glycol-based hydrogel. The hydrogel cell
suspensions, each at a density of 20 × 106 cells/mL, were
stratified into two separate layers that were molded into the shape and
dimensions of an adult human cadaveric mandibular condyle by sequential
photopolymerization. The osteochondral constructs fabricated in vitro were
implanted in the dorsum of immunodeficient mice for twelve weeks.
Results: De novo formation of articular condyles in the shape and
dimensions of the adult human mandibular condyle occurred after a twelve-week
period of in vivo implantation. Histological evaluation demonstrated two
stratified layers of cartilaginous and osseous tissues, and yet there was
mutual infiltration of cartilage-like and bone-like tissues into each other's
territories. The cartilaginous portion was stained intensively to safranin O
and expressed immunolocalized type-II collagen. Chondrocytes adjacent to the
tissue-engineered osteochondral junction were enlarged and expressed type-X
collagen, typical of hypertrophic chondrocytes. The osseous portion contained
bone trabeculae-like structures and expressed immunolocalized type-I collagen,
osteopontin, and osteonectin.
Conclusions: A cell encapsulation density of 20 million cells/mL
with in vivo incubation for twelve weeks yields further tissue maturation and
phenotypic growth of both cartilage-like and bone-like tissues in the
tissue-engineered articular condyle.
Clinical Relevance: Tissue engineering of an entire condyle with
chondral and osseous components derived from a single population of adult stem
cells, as described in the present study, may have therapeutic implications in
total joint replacement.