Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis

Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by cartilage degradation, synovitis, subchondral bone sclerosis and osteophyte formation. Current therapeutic approaches for OA are not curative and only temporarily alleviate symptoms. In recent years, pre-clinical experiments and clinical trials have demonstrated that mesenchymal stem cell (MSC) related therapy is a promising option for the treatment of cartilage lesions and OA. MSCs isolated from bone marrow (BMSCs) have been widely used in animal models and clinic practice to demonstrate their chondrogenic potential, however the incidence of BMSC donors is low. Adipose derived mesenchymal stem cells (AMSCs) are a more easily accessible source of stem cells for OA treatment. MSC related therapies for cartilage lesions and OA include tissue engineering of MSC transplantation, scaffold-free injection of stem cells and cell-free injection of exosomes into the injured joints. Although a great deal of effort is required at the basic and clinical research fronts, the promise is that improved cell-based therapies will ultimately lead to the repair of damaged or diseased joints, and MSC exosome therapy for OA could be a safer, cheaper and a more effective treatment modality. MSC related therapy is predicted to become a regular and routine regenerative medicine for OA treatment in future clinical practice.

Keywords: Mesenchymal stem cells; cartilage; exosomes; intra-articular injection; osteoarthritis; stem cell tissue engineering.

Figure 1

Schematic of MSC-based therapies for cartilage lesions and OA. The benefits of MSCs include their capacity to self-renew, differentiate, and to secrete growth factors and cytokines. The tissue engineering of MSCs seeded in hydrogel polymers induce cartilage regeneration and subchondral bone improvement; in very rare case, the cell transplantation is performed without the scaffold. The intra-articular injection of MSCs suspended in media play important roles in immunomodulation and reduced inflammation. Both of these therapies maintain cartilage and bone hemostasis and inhibit OA progression. The molecular mechanisms of MSC function involve the differential expression of anabolic and catabolic genes including collagen type II, MMP13, ADAMTS and VEGF, and secreted factors including IFN-γ, IL-10, TNF-α and IL-6. Upward red arrows indicate increased gene expression and downward red arrows indicate decreased gene expression.

Figure 2

Biogenesis of MSC exosomes and the function of intra-articular injection of MSC exosomes for OA treatment. A. MSC exosome biogenesis. Exosomes originate from the inward invagination of the plasma membrane, and are formed as multivesicular bodies (MVBs) which composed of intraluminal vesicles (ILVs). Exosomes are secreted by fusion of the MVB with the plasma membrane, while microvesicles are secreted through the forward budding of plasma membrane. B. The contents of exosomes include transmembrane proteins, internal proteins (cytosolic, cytoskeletal, and growth factors), internal lipids, internal miRNAs and mRNAs. C. The function of intra-articular injection of MSC exosomes for OA treatment including inhibiting cartilage degeneration (CD) and subchondral bone deterioration (SBD), reducing osteophyte formation (OF) and resisting synovial inflammation (IF).