Quality of Cartilage Repair from Marrow Stimulation Correlates with Cell Number, Clonogenic, Chondrogenic, and Matrix Production Potential of Underlying Bone Marrow Stromal Cells in a Rabbit Model

Abstract

Objective Previous studies have shown that intrinsic behavior of subchondral bone marrow stem cells (BMSCs) is influenced by donors and locations. To understand the variability in cartilage repair outcomes following bone marrow stimulation, we tested the hypothesis that in vivo cartilage repair correlates with in vitro biological properties of BMSCs using a rabbit model. Methods Full-thickness cartilage defects were created in the trochlea and condyle in one knee of skeletally mature New Zealand White rabbits ( n = 8) followed by microdrilling. Three-week repair tissues were analyzed by macroscopic International Cartilage Repair Society (ICRS) scores, O’Driscoll histological scores, and Safranin-O (Saf-O) and type-II collagen (Coll-II) % stain. BMSCs isolated from contralateral knees were assessed for cell yield, surface marker expression, CFU-f, %Saf-O, and %Coll-II in pellet culture followed by correlation analyses with the above cartilage repair responses. Results In vivo cartilage repair scores showed strong, positive correlation with cell number, clonogenic, chondrogenic, and matrix production (Coll-II, GAG) potential of in vitro TGF-βIII stimulated BMSC cultures. Trochlear repair showed clear evidence of donor dependency and strong correlation was observed for interdonor variation in repair and the above in vitro properties of trochlear BMSCs. Correlation analyses indicated that donor- and location-dependent variability observed in cartilage repair can be attributed to variation in the properties of BMSCs in underlying subchondral bone. Conclusion Variation in cell number, clonogenic, chondrogenic, and matrix production potential of BMSCs correlated with repair response observed in vivo and appear to be responsible for interanimal variability as well as location-dependent repair.

Injectable freeze‐dried chitosan‐platelet‐rich‐plasma implants improve marrow‐stimulated cartilage repair in a chronic‐defect rabbit model

“…Earlier studies have shown that PRP can induce a significant improvement in BMSC recruitment, angiogenesis (Simpson, Mills, & Noble, ; Veillette & McKee, ), expression of cartilage matrix (Smyth, Murawski, Fortier, Cole, & Kennedy, ), proliferation, and viability of chondrocytes and BMSCs (Lee, Park, Joung, Park, & Do, ; Park, Lee, Kim, Ahn, & Do, ) as well as stimulate migration and chondrogenic potential of subchondral BMSCs (Kruger et al, ). A strong influence of properties and potential of bone‐marrow‐derived stem cells in influencing cartilage repair has been demonstrated in the earlier studies (Dwivedi, Chevrier, Alameh, Hoemann, & Buschmann, ; Dwivedi, Chevrier, Hoemann, & Buschmann, ). Using an ovine chronic‐defect model, Milano et al showed that when used as an adjunct to BMS, PRP enhanced the repair response versus BMS alone (Milano et al, ).…”

“…Taken together, these factors may drive the superior repair response in presence of CS/PRP implants indicated by more hyaline nature of repair accompanied by better macroscopic regeneration and increased bone remodelling. Because the cartilage repair outcome is strongly influenced by the properties of BMSCs including their number, proliferation, and chondrogenic potential (Dwivedi, Chevrier, Alameh, et al, ), application of CS/PRP is also likely to improve the cartilage repair outcome with poor prognosis arising due to low cell number or reduced chondrogenic potential in older patient population or patients with older defects.…”

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

“…On the other hand, MSCs present in the SB are accessible through subchondral plate perforation and are believed to be responsible for limited cartilage regeneration following microfracture treatment of focal cartilage lesions (Dwivedi et al, 2018). In our previous work, we investigated SB MSCs in advanced knee OA and compared MSCs from the medial, commonly weight-bearing compartment, with the lateral side of the joint (Sanjurjo-Rodriguez et al, 2019).…”

Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial

“…Although cell dosages have been associated with morphological quality of repair tissue in cell-based procedures, 12,33 absence of dosage effect while demonstrating safe and efficient treatment has been shown up to 4 years for the current clinical trial. 4,[37][38][39] Here, we present the final assessment of the full study duration of 5 years.…”