Intra-Articular Mesenchymal Stem Cell Injection for Knee Osteoarthritis: Mechanisms and Clinical Evidence

Abstract

Knee osteoarthritis presents higher incidences than other joints, with increased prevalence during aging. It is a progressive process and may eventually lead to disability. Mesenchymal stem cells (MSCs) are expected to repair damaged issues due to trilineage potential, trophic effects, and immunomodulatory properties of MSCs. Intra-articular MSC injection was reported to treat knee osteoarthritis in many studies. This review focuses on several issues of intra-articular MSC injection for knee osteoarthritis, including doses of MSCs applied for injection and the possibility of cartilage regeneration following MSC injection. Intra-articular MSC injection induced hyaline-like cartilage regeneration, which could be seen by arthroscopy in several studies. Additionally, anatomical, biomechanical, and biochemical changes during aging and other causes participate in the development of knee osteoarthritis. Conversely, appropriate intervention based on these anatomical, biomechanical, biochemical, and functional properties and their interactions may postpone the progress of knee OA and facilitate cartilage repair induced by MSC injection. Hence, post-injection rehabilitation programs and related mechanisms are discussed.

Keywords: cartilage regeneration; cartilage repair; dose; human; hyaline cartilage; intra-articular injection; knee osteoarthritis; mesenchymal stem cells.

Figure 1

Schematic demonstration of different layers of articular (hyaline) cartilage and subchondral bone of human knee joint. Arrows indicate the outermost layer of articular (hyaline) cartilage, that is, the lamina splendens. In some literature, the lamina splendens is also referred to as “the surface zone.” The superficial zone contains thin collagen fibrils and the middle zone contains thin and thick collagen fibrils; the deep zone contains thick collagen fibrils and is, therefore, the most stress-resistant. (A). Traditional concepts suggest that the superficial/gliding zone contains collagen fibrils parallel to the surface of healthy hyaline cartilage (whereas the lamina splendens does not contain collagen fibrils and chondrocytes); (B). Current findings indicate that the superficial/gliding zone contains collagen fibrils oblique to the surface of healthy hyaline cartilage (and the lamina splendens contain interwoven collagen bundles, which are not shown in this figure). Notably, interwoven collagen bundles within the lamina splendens rarely integrate obliquely oriented collagen fibrils in the superficial zone, which implies no tight connection between the two layers. Such a feature provides limited resistance to tearing/peeling off this surface layer from underlying cartilage tissues during exercise/sports accidents.