Mesenchymal Stem Cells From Different Sources in Meniscus Repair and Regeneration

Abstract

Meniscus damage is a common trauma that often arises from sports injuries or menisci tissue degeneration. Current treatment methods focus on the repair, replacement, and regeneration of the meniscus to restore its original function. The advance of tissue engineering provides a novel approach to restore the unique structure of the meniscus. Recently, mesenchymal stem cells found in tissues including bone marrow, peripheral blood, fat, and articular cavity synovium have shown specific advantages in meniscus repair. Although various studies explore the use of stem cells in repairing meniscal injuries from different sources and demonstrate their potential for chondrogenic differentiation, their meniscal cartilage-forming properties are yet to be systematically compared. Therefore, this review aims to summarize and compare different sources of mesenchymal stem cells for meniscal repair and regeneration.

Keywords: meniscal regeneration; meniscal repair; meniscus; stem cell; tissue engineering.

FIGURE 1

Stem cells employed in meniscal repair studies. Stem cell research for meniscus repair shows a boom in the past decade, with a peak in 2017 for stem cell research of all kinds and then declining slightly. In this column diagram, different colors correspondingly represent article numbers of that year. Blue ones are less than 5 (5 is not included); gray ones are from 5 to 9; orange ones are from 10 to 14; brown ones are from 15 to 19; purple one is more than 20.

FIGURE 2

Trends in the number of stem cell studies on bone marrow mesenchymal stem cells, adipose-derived stem cells, and synovial mesenchymal stem cells.

FIGURE 3

Intra-articular injection of hMSC promoted regeneration of rat meniscus (A) Representative sections of the meniscus stained with Toluidine blue (top and middle), and immunostained for type II collagen (bottom) after PBS or hMSCs injection. The staining in the PBS-treated sample was less with Toluidine blue and the antibody for type II collagen. The schema of the meniscus on the left is shown for orientation. Scale bar, 100 μm. (B) Representative gross photographs (top) and sections (bottom) of the joint surface of the tibia at 8 weeks. The cartilage was stained with India ink to identify fibrillation and erosion. The white circle indicates the medial tibial plateau. The tibia was sectioned coronally and stained with safranin-O and fast green to identify cartilage (red). Scale bars, 2 mm (top) or 200 μm (bottom). (C) Quantification of histological analysis using the OARSI cartilage osteoarthritis histopathology grading system. Values are mean with lower and upper limit of 95% CI; n = 5 for each group (Mann–Whitney U test). Abbreviations: hMSC, human mesenchymal stem cell; rMSC, rat mesenchymal stem cell; N, native meniscus; R, regenerated meniscus; TB, Toluidine blue; Col II, type II collagen. Adapted with permission from Horie et al. (2012).

FIGURE 4

3D images of the cells distribution in scaffolds using different cell seeding methods. (A)–(D) Seeded with MSCs; (E)–(H) seeded with MFCs. (A),(E) Surface static seeding; (B),(F) injection seeding; (C),(G) centrifugal seeding; (D),(H) vacuum seeding. (Red, 0–100 μm; yellow, 100–200 μm; green, 200–300 μm; blue, 300–400 μm; purple, 400–500 μm). Adapted with permission from Zhang et al. (2015).

FIGURE 5

Histological and macroscopic observation of meniscal regeneration after the intra-articular injection of MSCs derived from Luc/LacZ transgenic rats. (A): Representative sections of normal meniscus and regenerated tissues in the synovium-MSC injection group stained with X-gal (and eosin as counter staining), toluidine blue, and immunostained with collagen type 2. Scale bar = 100 μm. (B) Representative macroscopic findings of the joint surface of femur and tibia 12 weeks after the synovium-MSC group and the control group. The cartilage was stained with India ink. Abbreviations: L, lateral; M, medial; MSCs, mesenchymal stem cells. Adapted with permission from Horie et al. (2009).

FIGURE 6

Graphical abstract of the scaffolds fabrication, cell culture and implantation of the tissue-engineered meniscus constructs in rabbit knee joint. Adapted with permission from Moradi et al. (2017).