Based on promising preliminary results in animal models and in ongoing

preclinical studies, mesenchymal stem cells and their derivatives represent a potential therapeutic intervention to treat AKI. Footnotes P- Reviewer: Camussi G, Duan SB, Jung JS S- Editor: Ji FF L- Editor: A E- Editor: Lu purchase Fingolimod YJ
Core tip: Knee osteoarthritis is a common medical condition in the elderly and the obese. Despite the variety of available conventional treatments for this disease, in recent years stem cell therapy has been applied in an ever increasing number of clinical cases. Therefore the aim of this review is to outline the latest advances in stem cell therapy as a non-pharmacologic treatment for knee osteoarthritis. It also emphasizes on some of the challenges associated with stem cell therapy regarding knee cartilage regeneration and chondrogenesis in vitro and in vivo. INTRODUCTION Osteoarthritis (OA) of the knee is a chronic, indolent disease that affects all genders, ages and races but is known to be most common in the elderly and in obese people. A degenerative disease of the connective tissue, it mainly affects the articular cartilage (Figure ​(Figure11)[1]. The definition of knee OA varies in reported studies and includes self-reported knee OA (obtained from a questionnaire), radiographic definitions of knee osteoarthritis, and symptomatic knee OA (self-reported

joint pain and radiographic evidence of OA)[2]. Symptoms may include joint pain, stiffness and tenderness. Furthermore, as the cartilage substance decreases,

the bone surface may also become affected. This results in development of osteophytes (bone spurs) and direct bone-bone contact. In addition to the stiffness of the joint, the patient tries to avoid pain by minimizing joint movement, which leads to muscle atrophy and laxity of the ligaments[1-4]. Figure 1 Pathophysiology of knee osteoarthritis. Comparison between a normal and diseased joint (Illustration created after Felson[3] and Buja et al[4]) The pathogenesis of knee OA have been linked to biomechanical and biochemical changes in the cartilage of the knee joint (e.g., inability to withstand Cilengitide normal mechanical stresses, limited supply of nutrients and oxygen, inadequate synthesis of extracellular matrix components, increased synthesis of tissue-destructive proteinases (matrix metalloproteinases and aggrecanases) and overall apoptosis of chondrocytes)[4-7]. Recently, synovial inflammation has also been accredited as a factor limiting knee cartilage repair. Moreover, it correlates to clinical signs of knee OA such as swelling of the knee and inflammatory pain[7,8]. It is believed that synovial inflammation is a response of synovial macrophages to cartilage debris and catabolic mediators entering the synovial cavity[8,9].