Cell Transplantation for Articular Cartilage Defects: Principles of Past, Present, and Future Practice

Abstract

As articular cartilage has very limited self-repair capability, the repair and regeneration of damaged cartilage is a major challenge. This review aims to outline the past, present, and future of cell therapies for articular cartilage defect repair. Autologous chondrocyte implantation (ACI) has been used clinically for more than 20 years, and the short, medium, and long-term clinical outcomes of three generation of ACI are extensively overviewed. Also, strategies of clinical outcome evaluation, ACI limitations, and the comparison of ACI clinical outcomes with those of other surgical techniques are discussed. Moreover, mesenchymal stem cells and pluripotent stem cells for cartilage regeneration in vitro, in vivo, and in a few clinical studies are reviewed. This review not only comprehensively analyzes the ACI clinical data but also considers the findings from state-of-the-art stem cell research on cartilage repair from bench and bedside. The conclusion provides clues for the future development of strategies for cartilage regeneration.

Origin and function of cartilage stem/progenitor cells in osteoarthritis

“…14,15 Thus, marrow-stimulation techniques such as microfracture have been clinically developed whereby penetration of the subchondral bone enables the bone marrow to seep into the cartilage defect area to form reparative cartilage, which usually consists of a structurally inferior fibrous tissue. 20 The existence of an endogenous population of progenitor or stem cells in articular cartilage that function as reparative cells, however, was considered questionable because articular cartilage is unable to heal effectively after injury. 13 The lack of a perichondrium and vasculature in articular cartilage also probably contribute to the nonreparative nature of this tissue, but neither transplantation of perichondrium nor connection of bone marrow with microfracture has been found to contribute to efficient articular cartilage repair.…”

Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy

“…What is more, according to the guideline from OA Research Society International published in 2014, the effect of intraarticular injection of hyaluronic acid, oral administration of glucosamine, and physiotherapies such as acupuncture and electrotherapy were uncertain even in symptom relief of OA and were not appropriate for disease modification (McAlindon et al, ). Moreover, except arthroplasty for end‐stage patients, surgical interventions such as mosaicplasty, microfracture, and autologous chondrocyte implantation not only induce donor site morbidity but also regenerate inferior fibrocartilage (Jiang, Zhang, Qi, Wang, & Ouyang, ). Hence, it is of great value to develop a remedy to circumvent the pathological process.…”

AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-β signal

“…2 Chondrocytes in articular cartilage can be damaged as a result of either traumatic mechanical destruction (automobile accidents and sports injuries) or progressive mechanical degeneration. 3 Unfortunately, damaged articular cartilage cannot be repaired due to several factors including restricted supply of blood, oxygen, and nutrients 4, 5 and restricted movement of neighboring chondrocytes to the defect area. 6 Therefore, several efforts, including cell-based therapies using chondrocytes or mesenchymal stem cells, have been made to repair cartilage defects.…”