Dataset Information

Xenotransplantation: Progress Along Paths Uncertain from Models to Application.

ABSTRACT: For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. In principle, use of animals such as pigs as a source of transplants would allow transplantation to exert a vastly greater impact than allotransplantation on medicine and public health. However, biological barriers to xenotransplantation, including immunity of the recipient, incompatibility of biological systems, and transmission of novel infectious agents, are believed to exceed the barriers to allotransplantation and presently to hinder clinical applications. One way potentially to address the barriers to xenotransplantation is by genetic engineering animal sources. The last 2 decades have brought progressive advances in approaches that can be applied to genetic modification of large animals. Application of these approaches to genetic engineering of pigs has contributed to dramatic improvement in the outcome of experimental xenografts in nonhuman primates and have encouraged the development of a new type of xenograft, a reverse xenograft, in which human stem cells are introduced into pigs under conditions that support differentiation and expansion into functional tissues and potentially organs. These advances make it appropriate to consider the potential limitation of genetic engineering and of current models for advancing the clinical applications of xenotransplantation and reverse xenotransplantation.

SUBMITTER: Platt JL

PROVIDER: S-EPMC6808066 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Xenotransplantation: Progress Along Paths Uncertain from Models to Application.

Platt Jeffrey L JL Cascalho Marilia M Piedrahita Jorge A JA

ILAR journal 20181201 3

For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. ...[more]

PMID: 30541147

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Project description:This study assessed the dispersal of five bacterial communities from contrasting compartments along a fractured clay till depth profile comprising plow layer soil, preferential flow paths (biopores and the tectonic fractures below), and matrix sediments, down to 350?cm below the surface. A recently developed expansion of the porous surface model (PSM) was used to capture bacterial communities dispersing under controlled hydration conditions on a soil-like surface. All five communities contained bacteria capable of active dispersal under relatively low hydration conditions (-3.1?kPa). Further testing of the plow layer community revealed active dispersal even at matric potentials of -6.3 to -8.4?kPa, previously thought to be too dry for dispersal on the PSM. Using 16S rRNA gene amplicon sequencing, the dispersing communities were found to be less diverse than their corresponding total communities. The dominant dispersers in most compartments belonged to the genus Pseudomonas and, in the plow layer soil, to Rahnella as well. An exception to this was the dispersing community in the matrix at 350?cm below the surface, which was dominated by Pantoea Hydrologically connected compartments shared proportionally more dispersing than nondispersing amplicon sequence variants (ASVs), suggesting that active dispersal is important for colonizing these compartments. These results highlight the importance of including soil profile heterogeneity when assessing the role of active dispersal and contribute to discerning the importance of active dispersal in the soil environment.IMPORTANCE The ability to disperse is considered essential for soil bacteria colonization and survival, yet very little is known about the dispersal ability of communities from different heterogeneous soil compartments. Important factors for dispersal are the thickness and connectivity of the liquid film between soil particles. The present results from a fractured clay till depth profile suggest that dispersal ability is common in various soil compartments and that most are dominated by a few dispersing taxa. Importantly, an increase in shared dispersers among the preferential flow paths of the clay till suggests that active dispersal plays a role in the successful colonization of these habitats.

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Xenotransplantation: Progress Along Paths Uncertain from Models to Application.

Publications

Xenotransplantation: Progress Along Paths Uncertain from Models to Application.

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