**3. MSCs in articular cartilage injury**

**Figure 1.** fracture healed well.

(A) A 32-year-old male underwent external fixation of an open tibial fracture. After surgery, no callus was observed in 6 months. (B, C) he underwent bone

212 Stromal Cells - Structure, Function, and Therapeutic Implications

marrow aspiration and percutaneous grafting directly into the nonunion site. (D, E) 6 months after the transplantation, frontal and lateral X-ray images indicated the

Due to the limited ability of proliferation capacity of chondrocytes, articular cartilage injury often causes progressive degeneration of the joint and OA, which is a serious health and economic problem [27]. The typical current treatment for this disorder is microfracture, which is a surgical technique that was developed 20 years ago. This treatment uses the body's own healing abilities to regenerate the chondral surface. However, the regenerated fibrocartilage often has poor mechanical properties compared with normal cartilage.

Recently, the MSC-based autogenous transplantation treatment was proposed, since the potential of the MSCs to differentiate into chondrocytes has been well-recognized [28]. Compared with allogeneic cells, generally, autogenous cartilage progenitor cells are more effective in the treatment of articular cartilage defect [29]. The emerging typical paradigm to apply MSCs in this disorder is [30]: (1) during the first operation, a cartilage biopsy is taken from areas of damaged cartilage within the ankle or knee; (2) chondrocytes are isolated from the biopsy via enzymatic digestion and cultured in 2D monolayer cultures; (3) monolayer culture-expanded chondrocytes are seeded on a collagen type I–III membrane; and (4) in the second operation, the cartilage lesion is prepared and the collagen membrane is cut to size, placed in the lesion and secured with fibrin glue.

To clarify whether donor MSCs indeed contribute to cartilage regeneration in vivo via a progenitor-mediated mechanism [31], Zwolanek et al. describe a novel cell tracking system based on genetic transgenic donor and corresponding cell marker, and the results showed that MSC could contribute to cartilage regeneration via a progenitor - or nonprogenitor mediated mechanism [31]. The study by Windt et al. in humans also produced similar results [32]. Further study found that chondrogenesis can be regulated by adjusting the time and concentration of TGF-β [33].

To further improve the efficiency of MSC-based treatment, combining bone marrow-derived MSCs with scaffold have been tried for the reconstruction of cartilage [34]. For example, Sadlik et al. reported that the scaffold-embedded MSC was implanted into the knee to repair cartilage through dry arthroscopy, and the tissue regeneration was successful [27]. In addition, other approaches, such as the stem cells cultured from the subpatellar fat pad of arthritis patients can also be induced to differentiate into chondrocytes, which are very similar to the normal chondrocytes [29]. Koga et al. also found that the transplantation of synovial MSCs (SMSCs) in a rabbit model resulted in a large number of cartilage matrix development, and they also observed that SMSCs differentiated into osteocytes deeper into the defect, but differentiated into chondrocytes on the surface [35].
