Low back pain is an increasingly prevalent symptom mainly associated with intervertebral disc (IVD) degeneration. It is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and annulus fibrosus fissure formatting, which finally results in the IVD herniation and related clinical symptoms. Hydrogels have been drawing increasing attention as the ideal candidates for IVD degeneration because of their unique properties such as biocompatibility, highly tunable mechanical properties, and especially the water absorption and retention ability resembling the normal NP tissue. Numerous innovative hydrogel polymers have been generated in the most recent years. This review article will first briefly describe the anatomy and pathophysiology of IVDs and current therapies with their limitations. Following that, the article introduces the hydrogel materials in the classification of their origins. Next, it reviews the recent hydrogel polymers explored for IVD regeneration and analyses what efforts have been made to overcome the existing limitations. Finally, the challenges and prospects of hydrogel‐based treatments for IVD tissue are also discussed. We believe that these novel hydrogel‐based strategies may shed light on new possibilities in IVD degeneration disease.
Background. The development of liver transplantation (LT) is increasingly being limited by the unavailability of liver grafts. Unique regenerative capacity of liver in response to injuries makes living-donor liver transplantation (LDLT) a feasible strategy to meet clinical demands. Serine hydroxymethyl-transferase 2 (SHMT2) serves as the key enzyme in the biosynthesis of glycine. Glycine affects the activity of mammalian target of rapamycin (mTOR), which is important for cellular growth and proliferation. In this study, the effects of SHMT2 on mouse liver regeneration were investigated using a classical partial hepatectomy (PH) model. Methods. In vivo, PH was performed on mice with or without knockdown of SHMT2. In vitro, SHMT2 was overexpressed in primary hepatocytes, which were cultured in customized Dulbecco’s modified eagle media and LY294002 (an Akt inhibitor). Relevant indexes of liver regeneration, cell proliferation, and Akt/mTOR signal pathways were analyzed. Results. After PH, the expression levels of SHMT2 fluctuated with time and knockdown of SHMT2 in vivo lowered the regenerative ability of liver, with reduced glycine levels compared to the scramble group. In addition, overexpression of SHMT2 in hepatocytes boosted glycine production while enhancing Akt/mTOR pathway activity. These results were validated by the application of LY294002 in vitro. Conclusions. SHMT2 can contribute to liver regeneration after PH, and this is likely related to the activation of Akt/mTOR signaling pathway by its metabolic product, glycine, in hepatocytes. These results might have therapeutic implications for the prognosis of patients undergoing hepatic resection or transplantation.
Background Seeding cells are key factors in cell-based cartilage tissue regeneration. Monoculture of either chondrocyte or mesenchymal stem cells has several limitations. In recent years, co-culture strategies have provided potential solutions. In this study, directly co-cultured rat costal chondrocytes (CCs) and human Wharton’s jelly mesenchymal stem (hWJMSCs) cells were evaluated as a candidate to regenerate articular cartilage. Methods Rat CCs are directly co-cultured with hWJMSCs in a pellet model at different ratios (3:1, 1:1, 1:3) for 21 days. The monoculture pellets were used as controls. RT-qPCR, biochemical assays, histological staining and evaluations were performed to analyze the chondrogenic differentiation of each group. The 1:1 ratio co-culture pellet group together with monoculture controls were implanted into the osteochondral defects made on the femoral grooves of the rats for 4, 8, 12 weeks. Then, macroscopic and histological evaluations were performed. Results Compared to rat CCs pellet group, 3:1 and 1:1 ratio group demonstrated similar extracellular matrix production but less hypertrophy intendency. Immunochemistry staining found the consistent results. RT-PCR analysis indicated that chondrogenesis was promoted in co-cultured rat CCs, while expressions of hypertrophic genes were inhibited. However, hWJMSCs showed only slightly improved in chondrogenesis but not significantly different in hypertrophic expressions. In vivo experiments showed that all the pellets filled the defects but co-culture pellets demonstrated reduced hypertrophy, better surrounding cartilage integration and appropriate subchondral bone remodeling. Conclusion Co-culture of rat CCs and hWJMSCs demonstrated stable chondrogenic phenotype and decreased hypertrophic intendency in both vitro and vivo. These results suggest this co-culture combination as a promising candidate in articular cartilage regeneration.
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