Preclinical Studies and Clinical Trials on Cell-Based Treatments for Meniscus Regeneration

Objective: This study aims at performing a thorough review of cell-based treatment strategies for meniscus regeneration in preclinical and clinical studies.Methods: The PubMed, Embase, and Web of Science databases were searched for relevant studies (both preclinical and clinical) published from the time of database construction to December 2022. Data related to cell-based therapies for in situ regeneration of the meniscus were extracted independently by two researchers. Assessment of risk of bias was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analyses based on the classification of different treatment strategies were performed.Results: A total of 5730 articles were retrieved, of which 72 preclinical studies and 6 clinical studies were included in this review. Mesenchymal stem cells (MSCs), especially bone marrow MSCs (BMSCs), were the most commonly used cell type. Among preclinical studies, rabbit was the most commonly used animal species, partial meniscectomy was the most commonly adopted injury pattern, and 12 weeks was the most frequently chosen final time point for assessing repair outcomes. A range of natural and synthetic materials were used to aid cell delivery as scaffolds, hydrogels, or other morphologies. In clinical trials, there was large variation in the dose of cells, ranging from 16 x 10(6) to 150 x 10(6) cells with an average of 41.52 x 10(6) cells.Conclusion: The selection of treatment strategy for meniscus repair should be based on the nature of the injury. Cell-based therapies incorporating various "combination" strategies such as co-culture, composite materials, and extra stimulation may offer greater promise than single strategies for effective meniscal tissue regeneration, restoring natural meniscal anisotropy, and eventually achieving clinical translation. Impact StatementThis review provides an up-to-date and comprehensive overview of preclinical and clinical studies that tested cell-based treatments for meniscus regeneration. It presents novel perspectives on studies published in the past 30 years, giving consideration to the cell sources and dose selection, delivery methods, extra stimulation, animal models and injury patterns, timing of outcome assessment, and histological and biomechanical outcomes, as well as a summary of findings for individual studies. These unique insights will help to shape future research on the repair of meniscus lesions and inform the clinical translation of new cell-based tissue engineering strategies.