Mesenchymal Stromal Cells for Aging Cartilage Regeneration: A Review

Abstract

Cartilage degeneration is a key feature of aging and osteoarthritis, characterized by the progressive deterioration of joint function, pain, and limited mobility. Current treatments focus on symptom relief, not cartilage regeneration. Mesenchymal stromal cells (MSCs) offer a promising therapeutic option due to their capability to differentiate into chondrocytes, modulate inflammation, and promote tissue regeneration. This review explores the potential of MSCs for cartilage regeneration, examining their biological properties, action mechanisms, and applications in preclinical and clinical settings. MSCs derived from bone marrow, adipose tissue, and other sources can self-renew and differentiate into multiple cell types. In aging cartilage, they aid in tissue regeneration by secreting growth factors and cytokines that enhance repair and modulate immune responses. Recent preclinical studies show that MSCs can restore cartilage integrity, reduce inflammation, and improve joint function, although clinical translation remains challenging due to limitations such as cell viability, scalability, and regulatory concerns. Advancements in MSC delivery, including scaffold-based approaches and engineered exosomes, may improve therapeutic effectiveness. Potential risks, such as tumorigenicity and immune rejection, are also discussed, emphasizing the need for optimized treatment protocols and large-scale clinical trials to develop effective, minimally invasive therapies for cartilage regeneration.

Keywords: aging; cartilage regeneration; mesenchymal stromal cells; osteoarthritis; regenerative medicine; tissue engineering.

Figure 1

Sources, properties, and therapeutic potential of mesenchymal stromal cells (MSCs) for osteoarthritis treatment. MSCs can be derived from adipose tissue, umbilical cord, bone marrow, placenta, and dental pulp. MSCs from these sources exhibit essential characteristics, including self-renewal and multipotency, and respond to specific signaling molecules (e.g., BMP, FGF, TGF-β, IGF-1, SOX9) that aid in their proliferation and differentiation. MSCs also possess immunomodulatory and anti-inflammatory properties, making them suitable for therapeutic applications. Upon differentiation, MSCs can become chondrocytes, cells critical for cartilage formation and maintenance. Chondrocytes produce key ECM components, including type II collagen and aggrecan, which are essential for joint health. The paracrine and immunomodulatory effects of MSCs, along with their differentiation potential, are utilized in treating osteoarthritis to alleviate inflammation, support tissue repair, and restore cartilage function. This approach offers a promising approach for managing joint degenerative diseases.

Figure 2

Optimal delivery methods for mesenchymal stromal cells (MSCs) in joint regeneration. The three main delivery methods are scaffold, extracellular vesicles, and hydrogels. Scaffolds are porous, supportive structures that enable MSCs to attach and proliferate, thereby maintaining cell viability and providing structural stability at the target site. Extracellular vesicles, which are cell-free particles derived from MSCs, contain signaling molecules (e.g., RNA, proteins) that facilitate tissue repair through intercellular communication, eliminating the need to introduce live cells. Hydrogels, gel-like materials that encapsulate MSCs, provide a hydrated environment that protects cells and enables their gradual release, supporting sustained therapeutic effects. These three delivery methods are directed toward the joint, representing their potential applications in regenerative treatments for conditions like osteoarthritis or cartilage damage. This figure highlights the adaptability of MSC-based therapies and the importance of selecting optimal delivery vehicles to enhance clinical outcomes.