Meniscus repair: up-to-date advances in stem cell-based therapy

Abstract

The meniscus is a semilunar fibrocartilage between the tibia and femur that is essential for the structural and functional integrity of the keen joint. In addition to pain and knee joint dysfunction, meniscus injuries can also lead to degenerative changes of the knee joint such as osteoarthritis, which further affect patient productivity and quality of life. However, with intrinsic avascular property, the tearing meniscus tends to be nonunion and the augmentation of post-injury meniscus repair has long time been a challenge. Stem cell-based therapy with potent regenerative properties has recently attracted much attention in repairing meniscus injuries, among which mesenchymal stem cells were most explored for their easy availability, trilineage differentiation potential, and immunomodulatory properties. Here, we summarize the advances and achievements in stem cell-based therapy for meniscus repair in the last 5 years. We also highlight the obstacles before their successful clinical translation and propose some perspectives for stem cell-based therapy in meniscus repair.

Keywords: Meniscus repair; Regenerative medicine; Stem cell therapy.

Fig. 1

A Anatomy of the meniscus viewed from above [66]. Reproduced with permission [66]. Copyright 2002, Wolters Kluwer Health, Inc. B Frontal section of the medial compartment of the knee following perfusion with India ink. Vascular red-red zone, avascular white-white zone, and in-between red-white zones are labeled [7]. Reproduced with permission [7]. Copyright 1982, SAGE Publications

Fig. 2

Establishment of healthy human articular cartilage-derived progenitor cell lines [91]. Illustrated diagram of procedure used to establish human cartilage progenitor cell lines. Healthy human cartilage was diced into small pieces and digested using pronase and collagenase. Released cells were washed and strained to remove clumps. Cells were seeded at low density and individual single-cell-derived colonies were separated and stabilized using SV-40 mediated delivery of large-T antigen. Reproduced under the terms of the CC BY-NC license [91]. Copyright 2018, Jayasuriya et al.

Fig. 3

A Anatomical reconstruction model of rabbit menisci in left knee [104]. B A typical model of 3D medial meniscal scaffold. C 3D-printed poly(e-caprolactone) (PCL) scaffold seeded with mesenchymal stem cells (scale bar represents 10 mm). D PCL scaffold (black arrow) implanted between femur and tibia, with medial collateral ligament (green arrow) reserved. Reproduced with permission [104]. Copyright 2017, SAGE Publications

Fig. 4

Schematic representation of the preparation process of the scaffolds [109]. Flow chart of the preparation of the A MECM gel, B KGN-containing PLGA microspheres, and C PCL/MECM-KGN µS scaffold; D Possible mechanism of meniscus regeneration. Enhanced mechanical strength, endogenous stem cells, and sustained releasing KGN contributed to meniscus regeneration in these experiments. Reproduced under the terms of the CC BY-NC license [109]. Copyright 2021, Li et al. MECM, meniscus extracellular matrix; KGN, kartogenin; PLGA, poly(lactic-co-glycolic) acid; µS, microspheres

Fig. 5

Procedure for transplantation of synovial MSCs onto the repaired meniscus [120]. A Whole blood after centrifugation to prepare autologous human serum. B Arthroscopic meniscal repair. C Synovium harvest with a pituitary rongeur. D Synovium tissues as an MSC source. E SMSCs 1 day after plating. F SMSCs 14 days after plating. G SMSC suspension in a syringe. H Arthroscopic transplantation of SMSCs. (I) SMSC suspension was placed onto the repaired meniscus. Reproduced under the terms of the CC BY-NC license [120]. Copyright 2019, Sekiya et al.