Background:Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult.Purpose:To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies.Study Design:Systematic review.Methods:A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based.Results:After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds.Conclusion:There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential.
Background: Anterior cruciate ligament (ACL) tear and meniscal injury often co-occur. The protective effect of early ACL reconstruction (ACLR) on meniscal injury and its repair is not clear. Critical literature review can support or change clinical strategies and identify gaps in the available evidence. Purpose: To assess the protective effect of ACLR on the meniscus and provide clinical guidelines for managing ACL tears and subsequent meniscal injury. We aimed to answer the following questions: (1) Does ACLR protect the meniscus from subsequent injury? (2) Does early ACLR reduce secondary meniscal injury compared with delayed ACLR? (3) Does ACLR protect the repaired meniscus? Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed through use of MEDLINE and Embase electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms included ACL, reconstruction, and meniscus. Studies describing primary ACLR and nonoperative treatment in adult patients were included, as well as studies indicating timing of ACLR. The included articles were assessed individually for risk of bias through use of the modified Cochrane Risk of Bias and MINORS (Methodological Index for Nonrandomized Studies) tools. Results: One level 2 randomized controlled trial and several level 3 and 4 studies indicated a protective effect of ACLR on meniscal injury compared with nonoperative treatment. There was weak (level 3) evidence of the protective effect of early ACLR on the meniscus. Meniscal repair failure was less frequent in patients with ACL reconstruction than in patients with ACL deficiency (level 4). Conclusion: The evidence collected in this review suggests a protective effect of ACLR for subsequent meniscal injury (level 2 evidence). ACLR should be performed within 3 months of injury (level 3 evidence). Meniscal injury requiring surgical repair in the ACL-deficient knee should be treated with repair accompanied by ACLR (level 3 evidence). The paucity of level 2 studies prevents the formation of guidelines based on level 1 evidence. There is a strong clinical need for randomized or prospective trials to provide guidelines on timing of ACLR and meniscal repair.
Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).
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