Knee osteoarthritis (OA) is a progressive joint disease associated with pain and disability, and current treatments do not restore damaged articular cartilage. Intra-articular mesenchymal stem/stromal cell (MSC) injection has emerged as a minimally invasive biologic therapy with potential chondroprotective and regenerative effects; however, its capacity for structural cartilage repair remains uncertain. This narrative review summarizes clinical outcomes, with a focus on MRI-based cartilage morphological findings after MSC injection for knee OA. A MEDLINE search through January 30, 2025 identified 53 eligible clinical studies evaluating intra-articular MSC injections for knee cartilage lesions or OA, including 20 studies with MRI-based cartilage assessments. Most studies demonstrated significant improvements in pain and function, with benefits observed within 3-6 months and maintained up to 12-24 months. MSC therapy was safe and well tolerated. MRI findings were heterogeneous: most studies showed no significant structural improvement, while a limited number of studies reported cartilage preservation or modest increases in cartilage thickness. Advanced MRI techniques, including T2 mapping, occasionally detected improvements in cartilage quality. Intra-articular MSC injection provides consistent clinical benefits for knee OA, but current MRI evidence suggests limited and variable morphological cartilage restoration. Further standardized studies are needed to clarify its regenerative potential.

Fibromyalgia remains a contested clinical entity, characterized by persistent uncertainty regarding its definition, diagnostic boundaries, and underlying mechanisms. Over the past three decades, diagnostic frameworks have evolved from the 1990 American College of Rheumatology (ACR) classification criteria, based on widespread pain and tender point examination, to symptom-based models emphasizing patient-reported outcomes, such as the 2010 and 2016 ACR criteria. While these developments have improved feasibility and expanded clinical recognition, they have largely remained confined to biomedical and neuropsychological domains. This narrative review critically examines the historical evolution, conceptual foundations, and methodological limitations of fibromyalgia diagnostic criteria, integrating evidence from major classification systems, including ACR frameworks and the ACTTION-American Pain Society (APS) Pain Taxonomy (AAPT). Across these models, fibromyalgia is predominantly operationalized through symptom aggregation, with limited incorporation of social and contextual determinants of health. The analysis highlights persistent epistemological tensions, including diagnostic inflation, the continuum of polysymptomatic distress, and debates regarding disease legitimacy. In response, emerging proposals advocate for a biopsychosocial diagnostic framework that formally integrates biological, psychological, and social dimensions into the diagnostic core. This review also critically evaluates alternative dual-framework approaches that separate biological diagnosis from psychosocial severity assessment, emphasizing potential limitations such as fragmentation of patient experience and underestimation of psychosocial mechanisms in symptom generation. The findings suggest that future diagnostic models should move beyond static, symptom-based thresholds toward dynamic, integrative, and context-sensitive approaches. Such models may improve patient stratification, clinical decision-making, and research validity, while aligning diagnostic practice with contemporary understandings of chronic pain as a multidimensional and interactive condition.

Articular cartilage defects of the knee remain a major clinical challenge because hyaline cartilage possesses very limited intrinsic healing capacity. Untreated lesions often lead to pain, functional impairment, and progressive joint degeneration. Autologous chondrocyte implantation (ACI) was introduced in the 1990s as a transformative joint-preserving surgery designed to promote hyaline-like cartilage regeneration rather than simple repair. Since its inception, ACI has undergone significant technical evolution across three generations. First-generation ACI utilized a periosteal flap to cover injected chondrocytes, which demonstrated the feasibility of biological repair but was hindered by complications such as periosteal hypertrophy. To address these issues, second-generation techniques introduced collagen membranes, improving procedural safety. The third generation, matrix-assisted autologous chondrocyte implantation (MACI), utilizes biodegradable scaffolds to ensure uniform cell distribution and simplified surgical workflows. In Japan, the development of atelocollagen-based scaffolds has further standardized these procedures, allowing for reliable clinical application. Historically, advanced age and early-stage osteoarthritis were considered relative or absolute contraindications for ACI due to concerns regarding diminished chondrocyte biological activity. However, contemporary clinical evidence indicates that chronological age alone is not a definitive predictor of treatment failure. While younger patients often achieve higher absolute clinical scores, middle-aged and older individuals frequently realize clinically meaningful improvements in pain relief and daily function. The success of ACI in these populations is increasingly linked to a comprehensive "whole-joint" management strategy, where concomitant pathologies such as limb malalignment, meniscal deficiency, and ligamentous instability are addressed simultaneously. By optimizing the overall joint environment, ACI serves as a potential intervention to delay the necessity of total knee arthroplasty in patients over the age of 40 or 50. Future perspectives in cartilage repair focus on the potential for one-stage cell-based therapies to reduce donor site morbidity and treatment complexity. One area of ongoing investigation involves the possible utilization of osteophyte-derived chondrocytes, which are typically discarded during surgery. Preliminary preclinical studies suggest that these cells may retain sufficient proliferative capacity and chondrogenic potential for therapeutic use. Integrating minced osteophyte cartilage with next-generation biomaterials could eventually offer a strategy that reduces the need for healthy cartilage biopsy and cell culture, though further clinical validation remains essential. In conclusion, ACI has transitioned from an experimental treatment into a versatile joint-preserving procedure. As research continues to refine surgical indications and explore alternative cell sources, ACI remains an important biological option for managing a broader spectrum of patients with degenerative cartilage pathology.

Host-pathogen interactions have shaped the evolution of the human immune system, sometimes resulting in genetic and acquired trade-offs between robust immunosurveillance and refined self-tolerance. This review examines four representative elements, HLA-B27, tyrosine kinase 2, IL-23 signaling, and anti-citrullinated protein antibodies, to illustrate how these immune components are balanced against the costs of autoimmune disorders. By tracing their evolutionary trajectories, molecular functions, and clinical implications, we aim to elucidate the double-edged nature of immune defense mechanisms and highlight therapeutic opportunities.