Three-dimensional (3D) in vitro pannus model for rheumatoid arthritis. During rheumatoid arthritis (RA), formation of an invasive pannus tissue in the synovial joints occurs. The pannus tissue ultimately leads to erosion of the underlying cartilage and even bone. Key players in pannus formation are the RA synovial fibroblasts (RASFs), showing an aggressive invasive behavior. For simulation of RA in the 3D in vitro pannus model, human chondrocytes are harvested from healthy donors and cultured for 2 weeks as high-density micromasses in 96-well plates. During this period, cartilage matrix formation occurs. Subsequently, micromasses are coated with human RASFs. After 14 days of coculture allowing intensive interactions of both cell types, the model can be used for the high-throughput screening of antirheumatic drugs. For automation, the CyBi™-Disk workstation (CyBio Inc., Jena, Germany) for parallel liquid handling is used.

PubMed entries for tissue engineering in the rheumatic diseases. (a) The first entry for the key word 'tissue engineering', also called 'regenerative medicine', in the National Center for Biotechnology database PubMed was in 1984. In 1994, 23 manuscripts were added, and 10 years later, 1,605 were added. In 2008, 2,706 entries for 'tissue engineering' and 688 for 'regenerative medicine' were introduced into PubMed. (b) The first two entries for both 'cartilage' and 'tissue engineering' or 'bone' and 'tissue engineering' were in 1991, accounting for 22% of all 'tissue engineering' and 'regenerative medicine' entries. Since that year, both values varied between approximately 15% and 30%. Surprisingly, the number of PubMed entries for 'tissue engineering' or 'regenerative medicine' and 'arthritis' (36 entries in 2007, which accounted for 1% of all 'tissue engineering' and 'regenerative medicine' entries) or 'osteoarthritis' (30 entries in 2007 or 0.9%) is very low and in recent years has not increased to a degree worth mentioning. (c) The number of entries for the key word 'mesenchymal stem cells' has also increased dramatically from 1 in 1991 to 1,140 in the first 7 months of 2008. From these 1,140 entries, only 25 were for 'arthritis' and 'mesenchymal stem cells' and 18 were for 'osteoarthritis' and 'mesenchymal stem cells'.

Cartilage tissue engineering with mesenchymal stem cells (MSCs) derived from osteoarthritis (OA) patients. Human MSCs were isolated and expanded from femoral heads of five OA patients undergoing endoprothetic joint replacement. (a) Two and a half million MSCs per 100 μL were embedded in fibrinogen PLGA fleeces and chondrogenically induced with transforming growth factor-beta-3. (b) At day 14, propidium iodide/fluorescein diacetate staining revealed a high cell viability (green cells) and homogenous cell distribution. Remaining PLGA fibers appeared red. (c) After 4 weeks, matrix formation was demonstrated by alcian blue staining of cartilage proteoglycans and by antibody staining of (d) collagen type I and (e) cartilage-specific collagen type II. (f) Negative IgG control. In summary, we found no differences between MSCs derived from healthy donors and those from patients with OA. PLGA, poly(DL-lactic acid-co-glycolic acid).