Introduction

Osteoarthritis (OA) is a common chronic disease and accounts for major physical pain and disability in older adults. It is assumed to be the fourth leading cause of disability in the world in 2020 [1]. OA consistently influences the knees, hips, hands, feet, and spine [2]. The knee is the most frequently affected site and accounts for almost 85% of the burden of OA worldwide, followed by the hand and hip [3–5]. The particular syndromes of OA encompass chronic pain, stiffness, mobility restriction, and joint tenderness [6]. A number of risk factors such as female sex, age, obesity, genetic factors, and Oxidative stress increase the chances of developing OA [7]. It is growing more prevalent today because of the combined factors of aging, obesity and the increasing numbers of damaged joints, and an estimated 250 million people are affected by this syndrome [1].

The structural variations in OA include articular cartilage, subchondral bone, ligaments, synovium, and periarticular muscles. The articular cartilage defect is the most obvious syndrome of OA, which is caused by degeneration of the extracellular matrix [8,9]. People diagnosed with OA suffer physical weakness, mental pressure and impaired quality of daily life [10]. Currently, both nonpharmacological methods and pharmacological methods are applied to treat OA. Nonpharmacological methods, including self-management, regular exercise, and weight control, are highly recommended and are regarded as first-line treatments for OA [11,12]. Pharmacological methods recommended in the guidelines are paracetamol and NSAIDs, which are often used when nonpharmacological methods are not able to relieve pain and reduce disability. Patients with hip and knee OA who do not respond to topical analgesics are recommended to take intra-articular corticosteroids [11]. Duloxetine is a serotonin and norepinephrine reuptake inhibitor, which is recommended in some guidelines to reduce the severe pain of OA [13]. New treatments, such as nerve growth factor (NGF) antibodies, have been evaluated and have shown positive results in reducing pain in patients with hip and knee OA [14]. Surgical options such as joint replacement surgery, knee osteotomy, and knee joint distraction are either recommended for patients with late-stage OA or young and energetic patients with moderate radiographic severity in OA [15-17]. However, the above treatments are designed to reduce pain and improve the mobility of joints instead of promoting the regeneration of damaged articular cartilage. The regenerative treatments are intended to repair and replace the injured cells and tissues with new ones. As a regenerative cell therapy of OA, mesenchymal stem cells (MSCs) have the potential of self-renewal and differentiation into cartilage and the capability of immune modulation. A number of preclinical and clinical studies have confirmed the potential for MSCs as a novel therapeutic strategy for the treatment of OA.

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