Induced Pluripotent Stem Cells as a Promising Path Toward Zone-Specific Meniscus Regeneration

For young and middle-aged patients with irreparable meniscal tears, preserving or restoring meniscal tissue is critical to maintaining joint function and delaying osteoarthritis. Yet, when repair is not feasible, partial meniscectomy remains common and can compromise the load-bearing function of the knee, underscoring a highly unmet medical need for regenerative strategies that restore functional tissue rather than simply relieve symptoms. Induced pluripotent stem cells (iPSCs) offer a scalable and potentially patient-matched source of progenitor cells for meniscal regeneration, with iPSC-derived cartilage already entering clinical study for articular cartilage defects. However, translating this progress to the meniscus presents a fundamental biological challenge: restoring a specialized, zonally organized tissue rather than simply generating sufficient cells. The meniscus is a structurally, mechanically, and biologically graded tissue with distinct inner, transitional, and outer zones. Consequently, generating fibrocartilage is unlikely to reproduce native meniscal function. In this review, we examine iPSC-based strategies through the framework of zone-specific meniscal regeneration, focusing on meniscal fibrochondrocyte generation and reconstruction of native tissue architecture. We compare biofabrication strategies against native structural, vascular, and mechanical benchmarks, and outline the preclinical, manufacturing and regulatory requirements for translating iPSC-derived meniscal constructs toward patient-centered clinical application.