Peripheral blood-derived mesenchymal stem cells in osteochondral repair: a perspective on emerging insights and future directions.

Mesenchymal stem cells (MSCs) isolated from peripheral blood (PB) are gaining increasing attention among both researchers and clinicians, representing a promising alternative to traditional stem cell sources such as bone marrow and adipose tissue. Their therapeutic use offers key advantages like high accessibility, minimally invasive collection and autologous nature of the graft. Together with the ability to differentiate into multiple cell types, PB-MSC features make them ideal candidates for a wide range of clinical applications in the fields of regenerative medicine, tissue engineering and immunotherapy. While the therapeutic potential of PB-derived MSCs is more and more acknowledged, several challenges still need to be overcome regarding, for example, their isolation, expansion, and differentiation efficiency. For clinical translation, PB-MSC administration may be specifically indicated when minimally invasive autologous cell therapies are required, especially when bone marrow harvest is not recommended due to age, comorbidity, or prior surgeries. Conversely, PB-MSC auto-transplant should be avoided in patients suffering from hematological malignancies, active infections, or bone marrow disorders, where circulating stem cell populations may be altered, or their isolation poses safety risks. In this Perspective, we highlight recent advances in PB-MSC isolation and characterization, discuss their bioengineering integration into osteochondral repair strategies, and examine their immunomodulatory potential in osteoarthritis (OA). We propose that PB-MSCs integrate regenerative and immunomodulatory properties, positioning them as a promising, autologous cell source for next-generation personalized regenerative therapies. However, their clinical translation critically depends on the development of reproducible, GMP-compliant expansion protocols and validated potency assays.