Coculture of engineered cartilage with primary chondrocytes induces expedited growth.
BACKGROUND
Soluble factors released from chondrocytes can both enhance and induce chondrocyte-like behavior in cocultured dedifferentiated cells. The ability to similarly prime and modulate biosynthetic activity of differentiated cells encapsulated in a three-dimensional environment is unknown.


OBJECTIVE
To understand the effect of coculture on engineered cartilage, we posed three hypotheses: (1) coculturing with a monolayer of chondrocytes ("chondrocyte feeder layer") expedites and increases engineered tissue growth; (2) expedited growth arises from paracrine effects; and (3) these effects are dependent on the specific morphology and expression of the two-dimensional feeder cells.


METHODS
In three separate studies, chondrocyte-laden hydrogels were cocultured with chondrocyte feeder layers. Mechanical properties and biochemical content were quantified to evaluate tissue properties. Histology and immunohistochemistry stains were observed to visualize each constituent's distribution and organization.


RESULTS
Coculture with a chondrocyte feeder layer led to stiffer tissue constructs (Young's modulus and dynamic modulus) with greater amounts of glycosaminoglycan and collagen. This was dependent on paracrine signaling between the two populations of cells and was directly modulated by the rounded morphology and expression of the feeder cell monolayer.


CONCLUSIONS
These findings suggest a potential need to prime and modulate tissues before implantation and present novel strategies for enhancing medium formulations using soluble factors released by feeder cells.


CONCLUSIONS
Determining the soluble factors present in the coculture system can enhance a chondrogenic medium formulation for improved growth of cartilage substitutes. The feeder layer strategy described here may also be used to prime donor cartilage allografts before implantation to increase their success in vivo.
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA.
Andrea R
AR
Tan
Elizabeth Y
EY
Dong
James P
JP
Andry
J Chloë
JC
Bulinski
Gerard A
GA
Ateshian
Clark T
CT
Hung
D000818:Animals; D001696:Biomechanical Phenomena; D002356:Cartilage / Q000378:metabolism* / Q000637:transplantation; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation; D020219:Chondrogenesis; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis; D055119:Elastic Modulus; D006025:Glycosaminoglycans / Q000096:biosynthesis; D020100:Hydrogels; D019899:Paracrine Communication; D013997:Time Factors; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D006025:Glycosaminoglycans; D020100:Hydrogels; D003094:Collagen
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