Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy

Abstract

Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three-dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications.

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

“…MSCs can be derived from blood by venous puncture or derived from bone marrow by, for example, aspiration from iliac crest or by surgical removal from a donor site, with increasing levels of invasiveness. The simplest means of cell delivery to the musculoskeletal system is direct injection of cells into the diseased tissue, under strict compliance with good medical practice [5,6]. Alternatively, MSCs can be harvested from blood, bone marrow or tissues and then maintained in tissue culture for amplification under controlled good medical practice conditions.…”

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

“…Although autologous chondrocytes have previously been used for the treatment of focal defects (4), their derivation requires additional surgical procedures leading to possible complications at the donor site (5). Adult stem cells are a promising alternative cell source due to their minimally invasive isolation and chondrogenic potential (6,7), but these cells also have limitations. The percentage of mesenchymal stem cells (MSCs) in bone marrow is low (8), whereas the more abundant adipose-derived stem cells (ASCs) appear to have reduced chondrogenic potential under current differentiation protocols (9).…”

Mesenchymal stem cell enhances chondral defects healing in horses

“…They present fibroblastic morphology and should adhere to plastic, show osteogenic, adipogenic and chondrogenic differentiation and express surface markers [6,7]. The benefits resulting from the use of MSC in chondral defects and osteoarthritis, such as tropism for injured cartilage, paracrine activity, cellular differentiation and proliferation, predict good results and more effective treatments [8][9][10].…”

“…MSC also reduce inflammatory cell infiltrate and provide cellular support during chondral repair. However, in spite of presenting good results, MSC implantation still face failures in the application, maintenance of cellular phenotype and evidence of effectiveness, particularly in the long-term [7,8,15].…”