- Meeting abstract
- Open Access
Engineered cells and cartilage healing
© BioMed Central Ltd 2001
- Received: 6 April 2001
- Published: 25 April 2001
- Mesenchymal Precursor
- Engineer Cartilage
- Mesenchymal Precursor Cell
- Chondrocyte Dedifferentiation
- Cartilage Transplant
In chronic joint diseases, inflammation causes an imbalance in cartilage matrix turnover shifting towards degradation. This process may be promoted by destructive invasion of synovial tissue into cartilage as well as a switch in chondrocyte physiology. Furthermore, we could demonstrate a decrease in the expression of morphogenic factors, which are possibly supporting homeostasis and are probably released by the synovium in its function as cartilage nursing tissue. Leading to progressive degradation and loss of the cartilaginous joint surface, chronic joint diseases eventually depend on replacement therapies.
In recent years, methods for biological reconstruction of the articular surfaces with engineered cartilage transplants evolved as an alternative to the established therapy of endoprosthetic arthroplasty. The basic principle of the various strategies is the delivery and integration of functionally active autologous chondrocytes or mesenchymal precursor cells within an appropriate carrier system further supported by differentiation promoting factors into the original anatomic site to restore tissue architecture and function.
Using in vitro preformed implants appears to be particularly promising. This cartilage engineering is usually based on application of biocompatible and resorbable embedding substances and/or scaffold materials. Results from gene expression analysis clearly favour three-dimensional instead of monolayer chondrocyte cultivation to enhance cartilage matrix production in vitro. Implants of such constructs in the cartilaginous environment of the joint in rabbits or horses were found to produce cartilage typic morphological patterns and matrix synthesis. Heterotopic implantation for example subcutaneously into immunocompromized nude mice may induce unspecific fibroblastoid invasion and implant destruction. Encapsulation experiments prevented this process of infiltration, leading to enhanced matrix production and cartilage formation.
As an alternative and avoiding artificial barriers, tissue maturation and stabilization may be supported by morphogenetic factors, which are representatives of the TGF-β family and key molecules in cartilage and joint formation during development. Clonally expanded bone morphogentic protein (BMP)-7 transgenic primary chondrocytes demonstrated a qualitative switch in collagen expression from type I towards type II when cultured in alginate beads. Other markers of chondrocyte dedifferentiation were down-regulated also. Implantation subcutaneaously into nude mice revealed almost complete exclusion of host fibroblasts from the engineered cartilage accompanied by improved implant maturation.
Thus, the present results demonstrate that current artificial cartilage transplants are already feasible for joint cartilage repair. Nevertheless, treatment of severe joint defects faces specific problems, which are continuously addressed in ongoing studies: the fixation and integration of engineered cartilage in joints; the transplant protection against chronic inflammatory degradation; and the required enormous mechanical stability.
These challenges are particularly addressed by the current developments of composite grafts consisting of bone and cartilage components for reconstruction of the subchondral bone. Furthermore, controlled use of morphogenetic growth factors will unfold great potential to stabilize transplants, promote regeneration and may also allow guided tissue repair starting from mesenchymal precursors or stem cells.