A Potency Assay for Assessing the Chondrogenic Efficiency of Bioactive Molecules in Human Cartilage in vivo

Abstract

Purpose: Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. T cells have been demonstrated to play a role in the development of OA in animal models. However, the exact mechanism underlying is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic gradings. Methods: Peripheral blood, synovial tissue and infrapatellar fat pad-infiltrating T cells were isolated from the tissue of patients undergoing total knee arthroplasty. The frequency of T cells and each T cell subpopulation was determined via flow cytometry. Radiographic gradings of each patient was determined using the Ahlbach classification system and then correlated with the frequency of each tissue-infiltrating T cell population. Results: Our results show that CD8þ T cells are increased in osteoarthritic patients with higher radiographic gradings. When peripheral blood CD8þ T cells were examined, we show that CD8þ T cells possess a significantly higher level of activation than its CD4þ T cell counterpart (p<0.0001). Conclusions: Our results suggest a role for activated peripheral blood CD8þ T cells in the development of knee osteoarthritis.

Nanoscale and Macroscale Scaffolds with Controlled-Release Polymeric Systems for Dental Craniomaxillofacial Tissue Engineering.

“…Attempts at restoring a diseased or damaged TMJ have relied on a range of biomaterial scaffold systems to specifically induce bone, cartilage, or synovial disc [151,152]. As with other tissues, cartilage induction from both chondrocytes and MSCs have been promoted with molecules such as FGF, TGF, PDGF, and IGF-1 [153][154][155]. A key limitation for cartilage regeneration has been a source of primary chondrocytes.…”

The Role of Mesenchymal Stromal Cells in the Management of Osteoarthritis of the Knee

“…Recently, another group estimated the levels of TSP-2 to evaluate the chondrogenic potency of a UC-MSC product (Cellistem®OA, Cells for Cells, Brazil) intended to be used in phase I/phase II RCT for knee OA [48]. Other scientific groups have shown that autologous culture-expanded chondrocytes could be embedded in collagen-1 and injected subcutaneously in nude mice to predict the potency of several bioactive molecules in promoting chondrogenesis [49]. For the first time, we have developed a chondrogenic potency assay for an allogeneic pooled bone marrow-derived MSC product (phBMMSCs, Stempeucel®).…”

Nanoscale and Macroscale Scaffolds with Controlled-Release Polymeric Systems for Dental Craniomaxillofacial Tissue Engineering

“…Attempts at restoring a diseased or damaged TMJ have relied on a range of biomaterial scaffold systems to specifically induce bone, cartilage, or synovial disc [151,152]. As with other tissues, cartilage induction from both chondrocytes and MSCs have been promoted with molecules such as FGF, TGF, PDGF, and IGF-1 [153,154,155]. A key limitation for cartilage regeneration has been a source of primary chondrocytes.…”