Current perspectives in stem cell therapies for osteoarthritis of the knee

Abstract

Mesenchymal stem cells (MSCs) are emerging as an attractive option for osteoarthritis (OA) of the knee joint, due to their marked disease-modifying ability and chondrogenic potential. MSCs can be isolated from various organ tissues, such as bone marrow, adipose tissue, synovium, umbilical cord blood, and articular cartilage with similar phenotypic characteristics but different proliferation and differentiation potentials. They can be differentiated into a variety of connective tissues such as bone, adipose tissue, cartilage, intervertebral discs, ligaments, and muscles. Although several studies have reported on the clinical efficacy of MSCs in knee OA, the results lack consistency. Furthermore, there is no consensus regarding the proper cell dosage and application method to achieve the optimal effect of stem cells. Therefore, the purpose of this study is to review the characteristics of various type of stem cells in knee OA, especially MSCs. Moreover, we summarize the clinical issues faced during the application of MSCs.

Accentuating the sources of mesenchymal stem cells as cellular therapy for osteoarthritis knees—a panoramic review

“…There is induced production of interleukin-1 receptor antagonist (IL-1Ra) molecule in significant concentration by the MSCs and these produced molecules execute the bioactivity of inhibiting IL-1 catabolism (12). This interesting biological approach renders symptomatic relief in pain (13,14). MSCs also support neoangiogenesis through VEGF-A, VEGF-D, HGF, IGF-1, PDGF, PIGF, IL-6, EPO, MCP-1 and cellular proliferation through KGF, FGF-2, VEGF, IGF, PDGF, HGF (11,14).…”

“…This interesting biological approach renders symptomatic relief in pain (13,14). MSCs also support neoangiogenesis through VEGF-A, VEGF-D, HGF, IGF-1, PDGF, PIGF, IL-6, EPO, MCP-1 and cellular proliferation through KGF, FGF-2, VEGF, IGF, PDGF, HGF (11,14). MSCs exerted enhanced chondroprotection through diminished pro-inflammatory mediator production and increased antiinflammatory cytokine production including IDO, PGE2, TGF-β, TSG-6, HGF, NO, HO-1, HLA-G.…”

“…MSCs exerted enhanced chondroprotection through diminished pro-inflammatory mediator production and increased antiinflammatory cytokine production including IDO, PGE2, TGF-β, TSG-6, HGF, NO, HO-1, HLA-G. They mediate their anti-apoptotic actions through VEGF, HGF, IGF-1, TGF-β, GM-CSF (12)(13)(14). A schematic diagram elaborating on the physiological action of MSC in immunomodulation of OA pathogenesis is given in Figure 1.…”

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

“…Over past decades, a plurality of studies have found that direct intracerebral (AD) and intraarticular (RA, OP, OA) injection of MSCs confers multiple benefits evidenced by three key features: (1) inflammation remission, (2) stimulation of neotissue formation, and (3) measurable improvements in behavioral outcomes. While these investigations are thoroughly reviewed elsewhere (Duncan and Valenzuela, 2017 ; Kim and Shon, 2020 ), we here discuss current developments toward maximizing the clinical usability and therapeutic potential of MSCs as they apply to AD, inflammatory arthritis, and OP.…”

Mesenchymal Stem Cell-Derived Exosomes and Their Therapeutic Potential for Osteoarthritis

“…Moreover, they mediate cartilage repair and scar tissue formation by promoting the secretion of several growth factors, such as epithelial growth factor, insulin-like growth factor-1, fibroblast growth factor, TGF-β, and vascular endothelial growth factor [ 17 ]. These therapeutic functions contribute to the paracrine and immunomodulatory effects of anti-inflammatory and chondroprotective mediators secreted by MSCs [ 19 , 20 ]. Although it has long been known that MSCs produce abundant growth factors and cytokines, some studies have reported that injected MSCs are largely cleared or caught, and hence, only partially act in the target tissue [ 21 , 22 ].…”