Osteochondral Regeneration Using Adipose Tissue-Derived Mesenchymal Stem Cells

Abstract

Osteoarthritis (OA) is a major joint disease that promotes locomotor deficiency during the middle- to old-age, with the associated disability potentially decreasing quality of life. Recently, surgical strategies to reconstruct both articular cartilage and subchondral bone for OA have been diligently investigated for restoring joint structure and function. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), which maintain pluripotency and self-proliferation ability, have recently received attention as a useful tool to regenerate osteocartilage for OA. In this review, several studies were described related to AT-MSC spheroids, with scaffold and scaffold-free three-dimensional (3D) constructs produced using "mold" or "Kenzan" methods for osteochondral regeneration. First, several examples of articular cartilage regeneration using AT-MSCs were introduced. Second, studies of osteochondral regeneration (not only cartilage but also subchondral bone) using AT-MSCs were described. Third, examples were presented wherein spheroids were produced using AT-MSCs for cartilage regeneration. Fourth, osteochondral regeneration following autologous implantation of AT-MSC scaffold-free 3D constructs, fabricated using the "mold" or "Kenzan" method, was considered. Finally, prospects of osteochondral regeneration by scaffold-free 3D constructs using AT-MSC spheroids were discussed.

Keywords: Kenzan method; adipose tissue-derived mesenchymal stem cells; cell construct; mold method; osteoarthritis; osteochondral regeneration; scaffold-free; spheroid.

Figure 1

The fabrication of scaffold-free adipose tissue-derived mesenchymal stem cell (AT-MSC) construct using the “mold”. (a) Spheroids are piled up into a “mold” and employed to fabricate scaffold-free columnar cell constructs. (b) Spheroids are cultured and matured in the “mold” to fuse. (c) The scaffold-free cell construct is retrieved from the “mold” and used for implantation and analysis. In this figure, half of the mold is illustrated for the convenience of explanation.

Figure 2

The production of scaffold-free AT-MSC constructs using the “mold” for osteochondral regeneration in vivo: (a) Scaffold-free cell construct and osteochondral defects are prepared for implantation. (b) A scaffold-free cell construct is implanted into an osteochondral defect. (c) AT-MSCs in the construct are differentiated to chondrocytes and osteocytes, followed by regeneration of articular cartilage in the surface layer and formation of subchondral bone in the deep layer at the implanted site.

Figure 3

The fabrication of scaffold-free AT-MSC constructs using the “Kenzan”. (a) Spheroids are skewered onto the “Kenzan” automatically using a bio-3D printer and employed to fabricate scaffold-free tubular cell constructs. (b) Spheroids are cultured on the microneedles of the “Kenzan” to fuse with each other. (c) The scaffold-free cell construct is retrieved from the “Kenzan” and additionally cultured on tubular support for further maturation.

Figure 4

The production of scaffold-free AT-MSC constructs using “Kenzan” for osteochondral regeneration in vivo: (a) Scaffold-free cell construct is prepared for implantation. (b) A scaffold-free cell construct is implanted into an osteochondral defect. (c) Mesenchymal stem cells (MSCs) in the construct are differentiated to chondrocytes and osteocytes, followed by regeneration of articular cartilage in the surface layer and formation of subchondral bone in the deep layer at the implanted site.