Journal Article

Chondrogenesis of Peripheral Blood-Derived Mesenchymal Stromal Cells

Migliorini, Filippo, Nallakumarasamy, Arulkumar, Muthu, Sathish, Jeyaraman, Naveen, Schäfer, Luise, Ratna, Harish V. K., Jeyaraman, Madhan

2026

Overview

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105+ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Animals / Aspartic acid / Biological products / Biomaterials / Blood / Cartilage / Cartilage (articular) / Cartilage diseases / CD105 antigen / CD29 antigen / CD34 antigen / CD44 antigen / Cell adhesion / Cell culture / Cell Differentiation / Cell proliferation / Cell self-renewal / Chondrocytes / Chondrogenesis / Collagen / Cryopreservation / Extracellular matrix / Flow cytometry / Hematopoietic stem cells / Hemopoiesis / Homeopathy / Humans / Hyaluronic acid / Immunogenicity / Immunomodulation / Leukocytes (granulocytic) / Macrophages / Materia medica and therapeutics / Medical research / Medicine, Experimental / Mesenchymal stem cells / Mesenchymal Stem Cells - cytology / Mesenchymal Stem Cells - metabolism / mesenchymal stromal cells / Osteoarthritis / peripheral blood / Progenitor cells / Regeneration / Review / SOX / Stem cells / Stromal cells / Therapeutics