Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis

Abstract

Introduction: Mesenchymal stem cells (MSCs) hold great promise for regenerative therapies in the musculoskeletal system. Although MSCs from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) have been extensively characterized, there is still debate as to the ideal source of MSCs for tissue-engineering applications in bone repair. Methods: MSCs were isolated from cortical bone fragments (CBF-MSCs) obtained from patients undergoing laminectomy, selected by fluorescence-activated cell sorting analysis, and tested for their potential to undergo mesodermic differentiation. CBF-MSCs were then compared with BM-MSCs and AD-MSCs for their colony-forming unit capability and osteogenic potential in both normoxia and hypoxia. After 2 and 4 weeks in inducing media, differentiation was assessed qualitatively and quantitatively by the evaluation of alkaline phosphatase (ALP) expression and mineral deposition (Von Kossa staining). Transcriptional activity of osteoblastogenesis-associated genes (Alp, RUNX2, Spp1, and Bglap) was also analyzed. Results: The cortical fraction of the bone contains a subset of cells positive for MSC-associated markers and capable of tri-lineage differentiation. The hypoxic conditions were generally more effective in inducing osteogenesis for the three cell lines. However, at 2 and 4 weeks, greater calcium deposition and ALP expression were observed in both hypoxic and normoxic conditions in CBF-MSCs compared with AD-and BM-MSCs. These functional observations were further corroborated by gene expression analysis, which showed a significant upregulation of Bglap, Alp, and Spp1, with a 22.50 (±4.55) -, 46.56 (±7.4)-, 71.46 (±4.16)-fold increase compared with their uninduced counterparts. Conclusions: This novel population of MSCs retains a greater biosynthetic activity in vitro, which was found increased in hypoxic conditions. The present study demonstrates that quantitative differences between MSCs retrieved from bone marrow, adipose, and the cortical portion of the bone with respect to their osteogenic potential exist and suggests the cortical bone as suitable candidate to use for orthopedic tissue engineering and regenerative medicine.

The Current Perspectives of Stem Cell Therapy in Orthopedic Surgery

“…Joseph et al (35) comprised human cortical bone fraction (CBF-MSCs), BM-MSCs and AD-MSCs, and declared that CBF-MSCs’s osteogenic potential was superior to BM-MSCs and AD-MSCs in normoxia and hypoxia. Veriter et al (36) used AD-MCSs in 11 patients with bone nonunion and 7 patients of nonhealing chronic wounds and obtained successful results in both of the situations and did not face with serious side effects or adverse events.…”

Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue

“…MSCs differentiate toward bone, cartilage, tendon, ligament, and muscle . MSCs can be recruited from multiple tissues surrounding the site of injury including the bone marrow or from other stem cells niches found in compact bone , muscle tendons' cuffs , and periosteum . However, MSCs alone are not sufficient to repair injured bone, the healing is a regulated process in which resident stromal, progenitor, and inflammatory cells orchestrate a complex signaling cascade that leads to repair and remodeling .…”

In vitro characterization of human articular chondrocytes and chondroprogenitors derived from normal and osteoarthritic knee joints

“…Although MSCs (due to inherent multipotency and high replicative potential) (4)and chondrocytes (tissue nativity making them safe for use) (5) are promising candidates; their current usage still warrants optimization. It has been reported that MSCs exhibit a tendency for increased osteogenesis in-vitro (6,7) and fibrocartilage formation in vivo (8–10). Similarly, the limitations that affect chondrocyte use (Autologous chondrocyte implantation) are graft hypertrophy and mixed fibro-hyaline formation (11,12).…”