Extracorporeal human lymphatic organs are expected to be excellent tools in the study of human molecular and cellular bases of the immunologic balance and tissue harmony. A rational approach and process to design a device and a procedure to recreate the human lymph node environment in vitro is described with emphasis on T-cell activation. Based on this approach, a bioreactor and a process supporting self-assembly of human lymphatic tissues due to proper emulation of human architecture and homeostasis could be developed.
Interleukin (IL)-10 is a well known anti-inflammatory and immunoregulatory cytokine, mainly released by, and acting on cells of the immune system such as monocytes, macrophages, T cells, NK cells, and B cells. IL-10 is also produced by a few connective tissue cell types including chondrocytes and is involved in processes such as connective tissue extracellular matrix remodelling, although it's exact function in articular cartilage remains unclear. This review article summarizes after a short insight into functions of IL-10 in the immune system most of the published literature on the role of IL-10 in articular cartilage homeostasis and disorders. A critical analysis of the present literature was undertaken leading to a survey of the significance of IL-10 in rheumatoid arthritis (RA), osteoarthritis (OA) and blood induced cartilage damage with particular focus on the direct impact of IL-10 on chondrocyte biology. IL-10 is up-regulated in RA and OA and therapeutic effects of IL-10 in experimental arthritis using several gene therapeutic approaches were reported, mainly through an immune cell mediated immunosuppression mechanism. Recently, a direct anti-inflammatory, -catabolic and -apoptotic potential of IL-10 in cartilage was described, suggesting a chondroprotective effect of IL-10, not only in RA and OA, but also in non-RA and non-systemic cartilage disorders. Chondroprotection by IL-10 may be a promising tool in arthritis therapy, as IL-10 plays a role in joint and cartilage immunoregulation and homeostasis. However, a crucial problem remains to be the optimisation of local and continuous therapeutic effective levels of IL-10 administration in the joint.
Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity and autologous articular chondrocytes availability. The use of nonarticular heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor-site morbidity and a comparable extracellular cartilage matrix synthesis profile to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes, and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfill regular articular cartilage functions requires further studies.
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