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Objective To investigate the role of bone marrow-derived mesenchymal stem cells (BMSCs) compounded with bioprotein gel (Bg) in repair of knee articular cartilage defects of rabbits.Methods Bilateral femoral condylar cartilage defect models (3.5 mm in diameter and 3 mm in depth) were established in 36 healthy New Zealand rabbits.Animals were divided into three groups of 12 rabbits each according to the random number table:BMSCs-Bg group,Bg group and blank control group.Effect of repair was evaluated by anatomic observation and histological examination at 4,8,12 and 16 weeks after operation and by articular cartilage histological hemi-quantitative scoring system.Results Hyaline-like cartilage was noted in BMSCs-Bg group at 4 weeks postoperatively,got close to the normal at 8 and 12 weeks and showed no disintegration at 16 weeks.Only fibrous tissue or fibrocartilage was observed in other 2 groups.In BMSCs-Bg group histology scores were (4.5 ± 0.1) points,(4.9 ± 0.1) points,(5.5 ± 0.1) points,and (6.2 ± 0.1) points respectively at 4,8,12 and 16 weeks,higher than those in other 2 groups (P ＜ 0.05).Besides,the histology scores were higher in Bg group than in blank control group but the differences were insignificant.Conclusion BMSCs-Bg compound can well repair the articular cartilage defect in a short-term period,when Bg contributes to cartilage generation as a good cell carrier.
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<p><b>BACKGROUND</b>Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.</p><p><b>METHODS</b>C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured.</p><p><b>RESULTS</b>Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05).</p><p><b>CONCLUSION</b>Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.</p>