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Homeostatic mini-intestines through scaffold-guided organoid morphogenesis
Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology
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. However, the approaches that are used at present to derive these organoids in three-dimensional matrices
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result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host–microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.
Miniature gut tubes grown in vitro from mouse intestinal stem cells are perfusable, can be colonized with microorganisms and exhibit a similar arrangement and diversity of specialized cell types to intestines in vivo.
Journal Article
Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
Before they are used in the clinical setting, the effectiveness of artificially produced human-derived tissue-engineered medical products should be verified in an immunodeficient animal model, such as severe combined immunodeficient mice. However, small animal models are not sufficient to evaluate large-sized products for human use. Thus, an immunodeficient large animal model is necessary in order to properly evaluate the clinical efficacy of human-derived tissue-engineered products, such as artificial grafts. Here we report the development of an immunodeficient pig model, the operational immunodeficient pig (OIDP), by surgically removing the thymus and spleen, and creating a controlled immunosuppressive protocol using a combination of drugs commonly used in the clinical setting. We find that this model allows the long-term accommodation of artificial human vascular grafts. The development of the OIDP is an essential step towards a comprehensive and clinically relevant evaluation of human cell regeneration strategies at the preclinical stage.
The development of tissue-engineered vascular grafts heavily relies on the availability of large animal models that allow long-term assessment of graft patency. Here Itoh et al. propose a novel model of immunodeficient pigs that allows long-term accommodation of human cell-derived three-dimensional bioprinted vascular tubes.
Journal Article
Miniature horses : cool pets!
\"Provides basic information about miniature horses and keeping them as pets\"--Provided by publisher.
Book
Welcome to the CRISPR zoo
Birds and bees are just the beginning for a burgeoning technology.
Journal Article
So Much More Than Art
Miniature canoes, houses and totems, and human figurines have been produced on the Northwest Coast since at least the sixteenth century. What has motivated Indigenous artists to produce these tiny artworks? Are they curios, toys, art, or something else? So Much More Than Art is a highly original exploration of this intricate cultural pursuit. Through case studies and conversations with contemporary Indigenous artists, Jack Davy uncovers the ways in which miniatures have functioned as crucial components of satirical opposition to colonial government, preservation of traditional techniques, and political and legal negotiation. This nuanced study of a hitherto misunderstood practice demonstrates the importance of miniaturization as a technique for communicating complex cultural ideas between generations and communities, and across the divide that separates Indigenous and settler societies. Most of all, So Much More Than Art is a testament to the cultural resilience of the Indigenous peoples of the Northwest Coast.
eBook
Exploring the Genetic Signature of Body Size in Yucatan Miniature Pig
Since being domesticated about 10,000-12,000 years ago, domestic pigs (Sus scrofa domesticus) have been selected for traits of economic importance, in particular large body size. However, Yucatan miniature pigs have been selected for small body size to withstand high temperature environment and for laboratory use. This renders the Yucatan miniature pig a valuable model for understanding the evolution of body size. We investigate the genetic signature for selection of body size in the Yucatan miniature pig. Phylogenetic distance of Yucatan miniature pig was compared to other large swine breeds (Yorkshire, Landrace, Duroc and wild boar). By estimating the XP-EHH statistic using re-sequencing data derived from 70 pigs, we were able to unravel the signatures of selection of body size. We found that both selections at the level of organism, and at the cellular level have occurred. Selection at the higher levels include feed intake, regulation of body weight and increase in mass while selection at the molecular level includes cell cycle and cell proliferation. Positively selected genes probed by XP-EHH may provide insight into the docile character and innate immunity as well as body size of Yucatan miniature pig.
Journal Article