ABSTRACT
Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.
ABSTRACT
BACKGROUND: The 3D printed polylactic-co-glycolicacid/nano-hydroxyapatite (PLGA/nHA) scaffold carrying human recombinant bone morphogenetic protein 2 (rhBMP-2)/chitosan (CS) sustained release tissue-engineering bone has good biological activity, mechanical properties, and biological activity of its controlled release rhBMP-2. OBJECTIVE: To investigate the repair of mandibular defects with PLGA/nHA scaffold/rhBMP-2/CS sustained release tissue-engineering bone manufactured using 3D bionic printing technology. METHODS: Animal models of bilateral critical mandibular bone defects were established in 27 New Zealand white rabbits, followed by implantation of a 3D-printed PLGA/nHA scaffold/rhBMP-2/CS sustained release tissue-engineering bone on one side (experimental side), and a 3D-printed PLGA/nHA scaffold on the other side (control side). Mandibular specimens were harvested at postoperative days 30, 60 and 90 to carry out cone-beam CT, Micro CT, histological and immunohistochemical examinations. RESULTS AND CONCLUSION: The results from micro-CT analysis revealed that the volume of newly formed bone volume and the amount of bone trabeculae on the experimental side were significantly higher than those on the control side at different postoperative time points (P ＜ 0.05). The results from cone-beam CT examination showed that at 90 postoperative days, bone density of the bone defect on the experimental side was close to that of the surrounding bone, new bone tissues were full of the original bone defect area, and the trabecular bone arranged regularly, while on the control side, worm-eaten discontinuous low-density osteoid tissues were visible in the bone defect area. Osteogenesis on the experimental side was better than that on the control side. Histological findings demonstrated that on the experimental side, a large amount of mature lamellae were detected in the bone defect area, with well-arranged trabecular bones and abundant capillaries, and moreover, the scaffold material had been completely absorbed. However, low-density, loose-meshed, irregular braided bone tissues with rare capillaries were observed on the control side, and the scaffold material had been mostly absorbed. Immunohistochemical findings indicated that the osteocalcin-dyed area on the experimental side was significantly larger than that of the control side at postoperative 90 days. To conclude, 3D-printed PLGA/nHA scaffold/rhBMP-2/CS sustained release tissue-engineering bone is favorable for the repair and reconstruction of experimental mandibular defects in rabbits.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of platelet-rich plasma (PRP) and latissimus dorsi myofascia with blood vessel on vascularization of tissue engineered bone in dogs.</p><p><b>METHODS</b>Bone marrow stromal cells (BMSCs) were isolated from iliac bone of dogs. PRP was obtained from the same dog. And demineralized bone matrix (DBM) were prepared from homologuous bone. ABCD 4 areas were divided on the back of dog. PRP/BMSCs/DBM was implanted around the vessels of lattisimus dorsi muscle in the A. PRP/BMSCs/DBM wrapped by superficial fascia in the B. BMSCs/DBM was implanted around vessels of lattisimus dorsi muscle in the C. BMSCs/DBM wrapped by superficial fascia in the D area of the same dog. 4, 8, 12 weeks after implantation, gross specimen and histology examination were made.</p><p><b>RESULTS</b>Osteogenesis and blood vessel formation results were A>B>C>D area.</p><p><b>CONCLUSION</b>The results suggested that the PRP and latissimus dorsi myofascia with blood vessels could promote calcification and vascularization in tissue-engineered bone.</p>
Subject(s)
Animals , Dogs , Biocompatible Materials , Bone and Bones , Mesenchymal Stem Cells , Osteogenesis , Platelet-Rich Plasma , Superficial Back Muscles , Tissue EngineeringABSTRACT
<p><b>OBJECTIVE</b>To study the effects of platelet rich plasma (PRP) on vascularization of tissue-engineered bone.</p><p><b>METHODS</b>Bone marrow stromal cell (BMSC) were isolated from iliac bone of dogs. PRP was obtained from the same dog and demineralized bone matrix (DBM) was prepared from homologous bone. Twelve dogs were divided into three groups and the back of each dog was divided into four areas. The DBM- BMSC- PRP was implanted in the area A and B; the DBM-BMSC without PRP was implanted in the area C and D. The implants in the areas A and C were wrapped using myo-fascia with blood vessel of latissimus dorsi. The implants in the area B and D were wrapped using superficial fascia of the back without blood vessel. The implants were taken out 4, 8 and 12 weeks later for examination.</p><p><b>RESULTS</b>The degree of calcification and blood vessel formation of the implants was A > B > C > D.</p><p><b>CONCLUSIONS</b>Both PRP and vessels of latissimus dorsi muscle could promote calcification and vascularization in tissue-engineered bone, when used separately or in combination.</p>