SUMMARY Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

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Metallic nanoparticles (such as gold and silver) have been intensely studied for wound healing applications due to their ability to be easily functionalized, possess antibacterial properties, and their strong potential for targeted drug release. In this study, rod-shaped silver nanorods (AgNRs) and gold nanorods (AuNRs) were fabricated by electron beam physical vapor deposition (EBPVD), and their cytotoxicity toward human skin fibroblasts were assessed and compared to sphere-shaped silver nanospheres (AgNSs) and gold nanospheres (AuNSs). Results showed that the 39.94 nm AgNSs showed the greatest toxicity with fibroblast cells followed by the 61.06 nm AuNSs, ∼556 nm × 47 nm (11.8:1 aspect ratio) AgNRs, and the ∼534 nm × 65 nm (8.2:1 aspect ratio) AuNRs demonstrated the least amount of toxicity. The calculated IC50 (50% inhibitory concentration) value for the AgNRs exposed to fibroblasts was greater after 4 days of exposure (387.3 μg mL(-1)) compared to the AgNSs and AuNSs (4.3 and 23.4 μg mL(-1), respectively), indicating that these spherical metallic nanoparticles displayed a greater toxicity to fibroblast cells. The IC50 value could not be measured for the AuNRs due to an incomplete dose response curve. The reduced cell toxicity with the presently developed rod-shaped nanoparticles suggests that they may be promising materials for use in numerous biomedical applications.

ContentsMore than eighteen years have passed since the first derivation of human embryonic stem cells (ESCs), but their clinical use is still met with several challenges, such as ethical concerns regarding the need of human embryos, tissue rejection after transplantation and tumour formation. The generation of human induced pluripotent stem cells (iPSCs) enables the access to patient-derived pluripotent stem cells (PSCs) and opens the door for personalized medicine as tissues/organs can potentially be generated from the same genetic background as the patient recipients, thus avoiding immune rejections or complication of immunosuppression strategies. In this regard, successful replacement, or augmentation, of the function of damaged tissue by patient-derived differentiated stem cells provides a promising cell replacement therapy for many devastating human diseases. Although human iPSCs can proliferate unlimitedly in culture and harbour the potential to generate all cell types in the adult body, currently, the functionality of differentiated cells is limited. An alternative strategy to realize the full potential of human iPSC for regenerative medicine is the in vivo tissue generation in large animal species via interspecies blastocyst complementation. As this technology is still in its infancy and there remains more questions than answers, thus in this review, we mainly focus the discussion on the conceptual framework, the emerging technologies and recent advances involved with interspecies blastocyst complementation, and will refer the readers to other more in-depth reviews on dynamic pluripotent stem cell states, genome editing and interspecies chimeras. Likewise, other emerging alternatives to combat the growing shortage of human organs, such as xenotransplantation or tissue engineering, topics that has been extensively reviewed, will not be covered here.