**5. MSCs in the treatment of osteoarthritis**

Osteoarthritis (OA) is a major cause of joint pain and loss of mobility in the elderly, which seriously affects the quality of life and causes huge social and economic burden. Many researchers have conducted a series of clinical studies on BMSCs transplantation to treat OA (**Table 1**), and these studies demonstrated that moderate confidence could be placed on the safety of MSCs therapy for knee OA, but the confidence in efficacy outcomes is low, mainly


a Auto\_BM\_MSC, Autologous Bone Marrow-derived MSCs. Auto\_AT\_MSC, Autologous Adipose Tissue-derived MSC. Allogeneic Bone Marrow-derived MSC.

b The WOMAC index (pain subscale) has been used; scale 0–100.

c The VAS index (pain subscale) has been used; scale 0–10.

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 dif-

Meniscus injury in the knee joint is probably the most frequent intra-articular damage. The typical treatment is a partial surgectomy, but it can lead to degeneration of articular cartilage, narrow joints, and early osteoarthritis. Intra-articular injection of MSCs could be a simple treatment with little damage since MSCs might promote the regeneration of meniscus. Indeed, it was found that when MSCs were injected directly into the articular cavity, they could migrate to the lesion site, directly participate in the tissue repair, and induce the repair of the host through the collateral secretion, and replace the injured tissue [36]. Murhpy et al. reported the first study of injection of BMSCs in sheep articular cavity [37], and observed the obvious repair of cartilage damage in meniscus injury, 6 and 12 weeks after injection. Whitehouse et al. also reported that undifferentiated MSCs/collagen-scaffold implant could provide a safe way to augment avascular meniscal repair in some patients [38]. Another study investigating the injection of allogenic MSCs in the context of post-subtotal meniscectomy found that there was evidence of meniscal regeneration in the two groups treated with MSCs [39]. However, Hong et al. used arthroscopic surgery to repair the meniscus of the posterior articular cavity with or without BMSCs after meniscus injury [40], and found that the meniscus and tibial plateau were not fully integrated, and the efficacy of MSCs treatment group was not significantly different from that of the control group. They argued that MSCs may differentiate into other tissue cells if they were not effectively induced to differentiate into specific cell types. Therefore, it is still a challenge to induce the cells into the meniscus carti-

Osteoarthritis (OA) is a major cause of joint pain and loss of mobility in the elderly, which seriously affects the quality of life and causes huge social and economic burden. Many researchers have conducted a series of clinical studies on BMSCs transplantation to treat OA (**Table 1**), and these studies demonstrated that moderate confidence could be placed on the safety of MSCs therapy for knee OA, but the confidence in efficacy outcomes is low, mainly

ferentiated into chondrocytes on the surface [35].

214 Stromal Cells - Structure, Function, and Therapeutic Implications

**4. MSCs in meniscus injury**

lage phenotype in this context.

**5. MSCs in the treatment of osteoarthritis**

**Table 1.** Summary of MSCs as the treatment of osteoarthritis.

due to limited clinical case number [46]. Therefore, further high-quality studies for OA with high internal and external validity are still required. In addition, Shi et al. compared the clinical results of platelet-rich plasma (PRP) and MSCs treatments for osteoarthritis of the knee in a systematic review and pointed out MSCS provide more significant disease therapeutic effect [47].
