Human pluripotent stem cells(PSCs)such as embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement.These human PSCs,similar to their counterparts of mouse,have the full potential to give rise to any type of cells in the body.However,for the promise to be fulfilled,it is necessary to convert these PSCs into functional specialized cells.Using the developmental principles of neural lineage specification,human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia,such as striatal gama-aminobutyric acid(GABA)-ergic neurons,spinal motor neurons and myelin sheath forming oligodendrocytes.The human PSCs,in general differentiate after the similar developmental program as that of the mouse:they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition.However,the human PSCs,unlike their counterparts of mouse,tend to respond divergently to the same set of extracellular signals at certain stages of differentiation,which will be a critical consideration to translate the animal model based studies to clinical application.
Memory by Engineered Mutagenesis with Optical In situ Readout（MEMOIR）is a novel strategy for lineage tracing that combines Cas9/g RNA and sequential multiplexed single-molecule RNA fluorescence hybridization（seqFISH）[1],which was created by Cai Long et al.at the California Institute of Technology[2].In MEMOIR,dynamic cellular event histories are recorded,then read out in single cells using seq FISH.Here,we introduce the
Objective：To investigate the effects of BCNU/PLGA microspheres on tumor growth,apoptosis and chemotherapy resistance in a C57BL/6 mice orthotopic brain glioma model using GL261 cell line.Methods：BCNU/PLGA sustained-release microspheres were prepared by the water-in-oil-in-water emulsion technique.GL261 cells were intracranially injected into C57BL/6 mouse by using the stereotactic technology.A total of 60 tumor-bearing mice were randomly and equally divided into three groups：untreated control,PLGA treated,BCNU/PLGA treated.Magnetic resonance imaging （MRI） was taken to evaluate tumor volume.BCNU/PLGA sustained-release wafers were implanted in the treatment group two weeks after inoculation.Survival time and quality were observed.Specimens were harvested,and immunohistochemical staining was used to check the expression of Bax,Bcl-2,and O6-methylguanine-DNA methyltransferase （MGMT）.Statistical methods was used for analysis of relevant data.Results：BCNU/PLGA sustained-release wafers were fabricated and implanted successfully.There is statistical difference of survival time between the BCNU/PLGA treated group and control groups （P＜0.05）.MRIscan showed inhibitory effect of BCNU/PLGA on tumor growth.Compared to the group A and B,BCNU/PLGA decreased the expression of apoptosis related gene Bcl-2 （P＜0.05）,but did not elevate the expression level of Bax （P＞0.05）,with the ratio of Bax/Bcl-2 increased.For MGMT protein expression,no statistically significant change was found in treated group （P＞0.05）.Conclusions：Local implantation of BCNU/PLGA microspheres improved the survival quality and time of GL261 glioma-bearing mice significandy,inhibited the tumor proliferation,induced more cell apoptosis,and did not increase the chemotherapy resistance.
