MXenes have attracted extensive attention due to their unique physicochemical properties. Especially, the flexibility and good conductivity endow MXenes with a great application prospect in the neural interfaces. However, the cytotoxicity of MXenes to nervous system remains unclear. In this study, we evaluated the cytotoxicity of Ti3C2 (the most studied MXenes) using primary neural stem cells (NSCs) and NSCs-derived differentiated cells in terms of apoptosis, viability, cellular uptake, cell membrane integrity, and global gene expression profiles. We found that 12.5 μg/mL Ti3C2 had no observable adverse effect on NSCs and NSCs-derived differentiated cells. However, 25 μg/mL Ti3C2 induced significant cytotoxicity and were internalized into the NSCs cells with compromised cell membrane. Furthermore, in the NSCs exposure to 25 μg/mL Ti3C2, we identified 198 differently expressed genes (DEGs), which were mainly associated with the extracellular region. Besides, the DEGs were involved in inflammatory, defense, stress, and stimulus response. This work will improve our understanding of biocompatibility of MXenes in the nervous system and promote the biomedical application of MXenes.

Hemangioblast, including primitive hematopoietic progenitor cells, play an important role in hematopoietic development, however, the underlying mechanism for the propagation of hematopoietic progenitor cells remains elusive. A variety of regulatory molecules activated in early embryonic development play a critical role in the maintenance of function of hematopoietic progenitor cells. Homeobox transcription factors are an important class of early embryonic developmental regulators determining hematopoietic development. However, the effect of homeobox protein Hox-B4 (HOXB4) ectopic expression on the development of hemangioblasts has not been fully addressed. This study aimed to investigate the role of Hoxb4a, an ortholog gene of HOXB4 in zebrafish, in the hematopoietic development in zebrafish. A transgenic zebrafish line was established with Cre-loxP system that stably overexpressed enhanced green fluorescent protein (EGFP)-tagged Hoxb4a protein under the control of hemangioblast-specific lmo2 promoter. Overexpression of Hoxb4a in the development of hemangioblasts resulted in a considerable increase in the number of stem cell leukemia (scl) and lmo2-positive primitive hematopoietic progenitor cells occurring in the posterior intermediate cell mass (ICM). Interestingly, Hoxb4a overexpression also disrupted the development of myelomonocytes in the anterior yolk sac and the posterior ICM, without affecting erythropoiesis in the posterior ICM. Taken together, these results indicate that Hoxb4a favours the development of hematopoietic progenitor cells originated from hemangioblasts in vivo.

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Graphene oxide (GO) has several potential biomedical applications and therefore cytotoxic evaluation of GO is very important. However, the two most common in vitro models for testing cytotoxicity—primary human cells and immortalized cell lines—suffer serious limitations, namely limited supplies of cells and unrealistic cellular responses, respectively. Here, we demonstrate the use of embryonic stem cell (ESC)‐derived cells to study GO cytotoxicity. We tested the use of retinal pigment epithelium (RPE) cells derived from three‐dimensional human ESC cultures (“ESC‐RPE” cells) as a model of GO cytotoxicity by exposing them to varying concentrations of GO nanosheets. For comparison, we also performed the same test with primary human retinal pigment epithelium cells (“hRPE”), and with cells derived from a human RPE cell line (“ARPE19” cells). We found that cytotoxicity metrics (viability, apoptosis, intracellular reactive oxygen species, and mitochondrial membrane potential) were very similar in ESC‐RPE cells and hRPE cells, and those in ARPE19 cells were very different. We conclude that cell models of GO cytotoxicity derived from ESCs are an excellent alternative to primary human cells, without the limitations of tissue availability.