Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression

Abstract

Cell-based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1-2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty. Superficial(C , top ∼ 500 µm) and deep cartilage(C ) was separated. Chondrogenic Connective Tissue Progenitors (CTP-C) were assayed by standardized Colony-Forming-Unit assay using automated image analysis (Colonyze ) based on ASTM standard F-2944-12. Cell concentration (cells/mg) was significantly greater in C (median: 7,000; range: 3,440-17,600) than C (median: 5,340; range: 3,393-9,660), p = 0.039. Prevalence (CTPs/million cells) was not different between C (median: 1,274; range: 0-3,898) and C (median:1,365; range:0-6,330), p = 0.42. In vitro performance of CTP-C progeny varied widely within and between patients, manifest by variation in colony size and morphology. Mean histopathological Mankin score was 4.7 (SD = 1.2), representing mild to moderate OA. Tidemark breach by blood vessels was associated with lower C cell concentration (p = 0.02). Matrix degradation was associated with lower C cell and CTP-C concentration (p = 0.015 and p = 0.095, respectively), independent of articular surface changes. These findings suggest that the initiation of OA may occur in either superficial or deep zones. The pathological changes affect CTP-Cs in C and C cartilage zones differently. The heterogeneity among the available CTP-Cs in C and C suggests performance-based selection to optimize cell-sourcing strategies for therapy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1728-1738, 2018.

Are Subchondral Intraosseous Injections Effective and Safe for the Treatment of Knee Osteoarthritis? A Systematic Review

“…6,9,11,14,15 Clinically, BMLs have been correlated to signs of joints surface deformation and increased symptoms of knee pain. 7,8,14,[16][17][18][19] BMLs may also serve as a risk factor for progression to end-stage disease. 1,9,11,14,18,20 Patients with BML have been reported to be nine times more likely to undergo total knee arthroplasty (TKA) in 3 years than patients without BML.…”

Biological potential alterations of migratory chondrogenic progenitor cells during knee osteoarthritic progression

“…First, the CPCs in grade 1-2 degenerative cartilages are not equated with the fully healthy CPCs. Second, we cannot exclude the possibility that CPC properties were influenced by anatomical (medial-to-lateral or superficial-to-deep) and/or mechanical differences in osteoarthritic cartilage [27]. Third, the cell surface markers of our ex vivo cultured mCPCs is different from that of in vitro culture-expanded [47].…”

“…Grade 1-2 cartilage includes cartilages with an intact surface (grade 1) and minimal fibrillation (grade 2), and grade 3-4 cartilage includes cartilage with fissures to subchondral bone [26]. The methods used to harvest the CPCs have been described in previous studies [5,12,27,28] with minor modifications. In brief, the cartilaginous tissues were separated from the osteoarthritic articular cartilages without contaminated subchondral bones and were minced into pieces (about 1.0 mm × 1.0 mm × 1.0 mm, Fig.…”

Proceedings of the signature series symposium “cellular therapies for orthopaedics and musculoskeletal disease proven and unproven therapies—promise, facts and fantasy,” international society for cellular therapies, montreal, canada, may 2, 2018

“…The success of cell transplantation will inevitably be dependent on the concentration, prevalence, biological attributes and biological potential of the cell population involved. However, no consensus has evolved regarding the optimal source of cells for cartilage repair, harvest or processing techniques, or critical quality attributes (CQAs) that predict future performance [49]. A particular limitation in cell transplantation is selection of a cell population that maintains an articular cartilage phenotype and does not undergo endochondral ossification over time [49À52].…”

“…To advance the quantitative use of colony-forming assays, the ASTM International has published Standard Test Method for automated colony-forming unit (CFU) assays; Image Acquisition and Analysis Method for Enumerating and Characterizing Cells and Colonies in Culture has been developed (ASTM InternationalÀF2944-12) [88]. Automated methods for colony analysis have been applied in recent publications [41À43, 49,89].…”