Regenerative and Cellular Therapies in Arthritis: Mechanisms, Clinical Evidence and Translational Challenges

Abstract

Background: Arthritis, and especially osteoarthritis and rheumatoid arthritis, contribute to chronic pain and disability and diminished quality of life on a global scale. Treatment approaches that are used currently seem to be based mainly on treating the symptoms without repairing the structures or modifying the disease, making regenerative approaches important. Aim: This review will synthesize and critically assess regenerative and cellular therapies in arthritis, their mechanisms, clinical trials, limitations, and potential to be used in translation. Materials and Methods: A comprehensive narrative literature review was conducted using electronic databases, including PubMed, Scopus, and Web of Science. The review comprised preclinical studies, randomized controlled trials, and clinical studies focusing on cell-based therapies, biological adjuncts, tissue engineering strategies, and gene therapy approaches in arthritis. Relevant articles published between 2010 and 2026 were identified using keywords such as “arthritis,” “mesenchymal stem cells,” “regenerative therapy,” “platelet-rich plasma,” and “extracellular vesicles,” with Boolean operators applied to refine the search. Studies were selected based on relevance, methodological quality, and availability in English, while non-relevant and non-peer-reviewed articles were excluded. Findings: The therapies derived from mesenchymal stem cells, autologous chondrocyte implantation, and induced pluripotent stem cells show promise in terms of cartilage regeneration and immunomodulation. The cell-free strategies, such as platelet-rich plasma, as well as extracellular vesicles, have promising anti-inflammatory and regenerative properties. Better therapeutic outcomes are achieved through the use of biomaterial scaffolds, tissue engineering, and gene therapy. Nevertheless, the clinical evidence is still divided, and some of the shortcomings comprise cell source variations, the absence of standardized protocols, nonuniform outcome measures, and the paucity of long-term data. Conclusion: Regenerative therapies are a promising transition to disease-modifying therapy in arthritis. Nonetheless, successful clinical translation depends on them, and there is a need for standardization of cell characterization, harmonization of clinical endpoints, scalability of production, and effective long-term clinical trials. The development of multimodal and combination interventions can also enhance the efficiency of the therapy process to further develop and become a means of its transfer to clinical practice.