The fate of implanted autologous chondrocytes in regenerated articular cartilage

Abstract

Autologous chondrocyte implantation (ACI) is used to treat some articular cartilage defects. However, the fate of the cultured chondrocytes after in-vivo transplantation and their role in cartilage regeneration remains unclear. To monitor the survival and fate of such cells in vivo, the chondrocytes were labelled with a lipophilic dye and the resultant regenerated tissue in dogs examined. It was found that, 4 weeks after implantation, the osteochondral defects were filled with regenerative tissue that resembled hyaline cartilage. Fluorescence microscopy of frozen sections of the regenerated tissue revealed that the majority of cells were derived from the DiI-labelled implanted chondrocytes. From these results, it was concluded that a large population of implanted autologous chondrocytes can survive at least 4 weeks after implantation and play a direct role in cartilage regeneration. However, it remains unknown whether other cells, such as periosteal cells or bone marrow stromal stem cells, are involved in the regeneration of cartilage after ACI.

Autologous Chondrocyte Transplantation in the Repair of Full-Thickness Focal Cartilage Damage in Rabbits

“…The transplanted chondrocytes can remain viable for a long time. [23][24][25][26] They can be traced using radioisotope cell labelling or fluorescence cell labelling and visualised using fluorescent or confocal microscopy or polymerase chain reaction. A mean of 87% of cell viability is maintained for up to 4 weeks; only 14% of the one million chondrocytes transplanted remained, but the total numbers of cells increase with time.…”

“…This suggests that ACT keeps the transplanted chondrocytes viable and promotes cell migration from the surrounding tissues. [23][24][25] Nonetheless, the source and fate of these cells were not determined. They may migrate into the surrounding tissues, participate in cell-mediated immune death or even in apoptosis.…”

“…Long-term survival of transplanted chondrocytes is difficult to follow because of (1) degradation of fluorescent dyes and (2) chondrocytes losing tagged dyes in their progeny when undergoing in vivo proliferation/differentiation. 27 ACT is preferred over subchondral drilling and mosaicplasty as a treatment of choice, 13 but the high cost incurred does not justify its use in standard practice. Subchondral drilling creates channels connecting marrow into the defects and enables mesenchymal-cell migration and differentiation into mature chondrocytes to promote cartilage repair.…”

Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow-Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant

“…Considerable efforts have been made to develop suitable cartilage repair procedures resulting in defect filling and restoration of the articular surface with the best possible tissue repair. There is evidence to support the idea that application of ex vivo expanded chondrocytes or mesenchymal stromal cells (MSCs) are relevant for cell-based therapies [ 2 , 3 ]. However, use of chondrocytes has several drawbacks such as a two-stage surgical procedure that may cause further cartilage damage and degeneration and chondrocyte dedifferentiation during in vitro culture.…”

Autologous Chondrocyte Implantation for Knee Focal Cartilage Defects: 3 Years’ Follow-Up at the University Malaya Medical Centre

“…Based on available literature, it appears that the repair process following implantation of autologous chondrocytes may be the result of multiple biological and mechanistic cellular functions acting in concert (27). It has been suggested that among those most commonly described, the repopulation of implanted chondrocytes within the defect sites appears to be the more accepted notion (28).…”