Progress of co-culture systems in cartilage regeneration

ABSTRACT

Introduction: Cartilage tissue engineering has rapidly developed in recent decades, exhibiting promising potential to regenerate and repair cartilage. However, the origin of a large amount of a suitable seed cell source is the major bottleneck for the further clinical application of cartilage tissue engineering. The use of a monoculture of passaged chondrocytes or mesenchymal stem cells results in undesired outcomes, such as fibrocartilage formation and hypertrophy. In the last two decades, co-cultures of chondrocytes and a variety of mesenchymal stem cells have been intensively investigated in vitro and in vivo, shedding light on the perspective of co-culture in cartilage tissue engineering.

Areas covered: We summarize the recent literature on the application of heterologous cell co-culture systems in cartilage tissue engineering and compare the differences between direct and indirect co-culture systems as well as discuss the underlying mechanisms.

Expert opinion: Co-culture system is proven to address many issues encountered by monocultures in cartilage tissue engineering, including reducing the number of chondrocytes needed and alleviating the dedifferentiation of chondrocytes. With the further development and knowledge of biomaterials, cartilage tissue engineering that combines the co-culture system and advanced biomaterials is expected to solve the difficult problem regarding the regeneration of functional cartilage.

KEYWORDS:

• Co-culture
• chondrogenesis
• mesenchymal stem cells
• cartilage regeneration

Article highlights

• Co-culture system can reduce the number of chondrocytes needed.

• Chondrocytes in the co-culture system secrete various soluble factors to enhance chondrogenesis.

• MSCs in the co-culture system excrete the trophic factors to stimulate chondrocyte proliferation.

• Gap junctions are of great importance in cell–cell connections by the exchange of nutrients and the transduction of molecular signals.

• Cartilage tissue engineering that combines the co-culture system and advanced biomaterials is promising for cartilage repair.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by Science and Technology Program of Guangzhou, China [grant number 201804010479], Key Programme for Scientific Research Project of Guangzhou Colleges and Universities [grant number 1201610097].