**1. Introduction**

Osteoarthritis (OA) is a whole organ disease characterized by the destruction or degeneration of articular cartilage, which is one of the most widespread and frequent chronic diseases and public health issues worldwide [1, 2]. During the course of OA, inflammatory response is a pivotal factor resulting in cartilage destruction or exacerbation of symptoms [2–4]. As satisfactory osteochondral repair, it's of great importance for the zonal restoration of adjacent cartilage and the subchondral bone [5]. For the past decades, despite the significant number of progress have been

achieved by multidisciplinary strategies such as surgeries (e.g., microfracture, mosaicplasty), autologous chondrocyte implantation (ACI), joint lubricants (e.g., hyaluronic acid), antiinflammatory drugs (e.g., NSAIDs) as well as cytotherapies (e.g., autologous chondrocyte implantation), the inherent limitations of regeneration and self-repair capacity in OA individuals still largely hinder the remission of the degeneration of articular cartilage [4, 6–8]. For example, even though joint replacement serves as an effective remedy for symptomatic end-stage disease including OA, most of the functional outcomes in patients are unsatisfactory and the lifespan of prosthesis is also largely limited [2, 9]. Distinguishing from the traditional remedies, cell-based strategies have emerged as an alternative with promising prospective in the treatment of OA and cartilage defects [10, 11].

State-of-the-art updates have turned to MSC-based cytotherapy for OA management both clinically and preclinically [5, 12]. The multifaceted superiorities of MSCs including multidirectional differentiation, high portability property, and low immunogenicity have made themselves ideal seed cells for OA treatment [3]. Meanwhile, MSCs or the derivatives are often encapsulated into natural or synthetic hydrogels, which can function by providing tunable biodegradability, and biocompatibility or enhancing cell vitality and functionality [10].

Herein, we mainly focus on the recent literatures relating to the application of MSCs for OA treatment based on the chondrogenic differentiation, and antiinflammatory and immunomodulatory effects of MSCs with or without biological scaffolds for cartilage regeneration. Meanwhile, we further discuss the promising prospective and formidable challenges of MSC-based cytotherapy in cartilage repair and regeneration as well.
