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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. Ques...

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Published in:Clinical orthopaedics and related research 2011-10, Vol.469 (10), p.2735-2743
Main Authors: Tan, Andrea R., Dong, Elizabeth Y., Andry, James P., Bulinski, J. Chloë, Ateshian, Gerard A., Hung, Clark T.
Format: Article
Language:English
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Summary: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. Questions/purposes 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. Clinical Relevance 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.
ISSN:0009-921X
1528-1132
DOI:10.1007/s11999-011-1772-7