Blastocyst-like embryo surrogates from stem cells in implantation models

Successful embryo implantation requires highly coordinated maternal-embryo interactions.Implantation failure is a major factor contributing to infertility.However,the mechanism underlying implantation failure remains unclear.An improved understanding of the early implantation process not only improves the success rate of assisted reproductive treatments but also helps in studying the pathophysiology of reproductive disorders.Owing to ethical concerns,in vivo studies of human embryo implantation are not feasible.However,the results obtained from animal models cannot be directly applied to humans.Over the years,in vitro implantation models have been developed to investigate implantation mechanisms.In this review,we discuss the use of different models for generating embryo-like surrogates to study early embryo development and implantation in vitro,with a specific focus on stem cell-derived blastocyst-like embryo surrogates.There is no definitive evidence that the recently established embryo-like models re-capitulate all developmental events of human embryos during the peri-implantation stage.Regardless,stem cell-derived embryo surrogates are the most valuable tools for studying the mechanisms of early cell lineage differentiation and developmental failures during implantation.

Modeling of Inner Surface Modification of a Cylindrical Tube by Plasma-Based Low-Energy Ion Implantation

The inner surface modification process by plasma-based low-energy ion implantation（PBLEII）with an electron cyclotron resonance（ECR）microwave plasma source located at the central axis of a cylindrical tube is modeled to optimize the low-energy ion implantation parameters for industrial applications.In this paper,a magnetized plasma diffusion fluid model has been established to describe the plasma nonuniformity caused by plasma diffusion under an axial magnetic field during the pulse-off time of low pulsed negative bias.Using this plasma density distribution as the initial condition,a sheath collisional fluid model is built up to describe the sheath evolution and ion implantation during the pulse-on time.The plasma nonuniformity at the end of the pulse-off time is more apparent along the radial direction compared with that in the axial direction due to the geometry of the linear plasma source in the center and the difference between perpendicular and parallel plasma diffusion coefficients with respect to the magnetic field.The normalized nitrogen plasma densities on the inner and outer surfaces of the tube are observed to be about 0.39 and 0.24,respectively,of which the value is 1 at the central plasma source.After a 5μs pulse-on time,in the area less than 2 cm from the end of the tube,the nitrogen ion implantation energy decreases from 1.5 keV to 1.3 keV and the ion implantation angle increases from several degrees to more than 40°;both variations reduce the nitrogen ion implantation depth.However,the nitrogen ion implantation dose peaks of about 2×10^（10）-7×10^（10）ions/cm^2 in this area are 2-4 times higher than that of 1.18×10^（10）ions/cm^2 and 1.63×10^（10）ions/cm^2 on the inner and outer surfaces of the tube.The sufficient ion implantation dose ensures an acceptable modification effect near the end of the tube under the low energy and large angle conditions for nitrogen ion implantation,because the modification effect is mainly determined by the ion implantation dose,just as the mass transfer process in PBLEII is dominated by low-energy ion implantation and thermal diffusion.Therefore,a comparatively uniform surface modification by the low-energy nitrogen ion implantation is achieved along the cylindrical tube on both the inner and outer surfaces.

Microencapsulated tumor assay:Evaluation of the nude mouse model of pancreatic cancer

AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed ona weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful im- plantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method displayed an obvious advantage in tumor mass (4th wk: 0.0461 ± 0.0399 vs 0.0313 ± 0.021, t = -0.81, P = 0.4379; 8th wk: 0.1284 ± 0.0284 vs 0.0943 ± 0.0571, t = -2.28, respectively, P = 0.0457) compared with the latter in the orthotopic implantation model. CONCLUSION: Encapsulation of pancreatic tumor cells is a reliable method for establishing a pancreatic tumor animal model.