Xenotransplantation as a model of integrated, multidisciplinary research

Cozzi, Emanuele; Bosio, Erika; Seveso, M; Rubello, Domenico; Ancona, Ermanno

doi:10.4161/org.7578

Cited by 20 publications

(13 citation statements)

References 92 publications

(101 reference statements)

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“…The pig has been frequently noted as a superior biologically relevant model, with anatomy and physiology comparable to humans [3], [4], and also provides appropriate xeno-transplantation sources and a model for study of human diseases [5]–[8]. Generation of porcine iPS cells complements studies of human iPS cells [9], [10], as the safety and effectiveness of iPS cells for therapeutics not only can be evaluated by genomic and epigenomics, but also can be functionally assessed by cell transplantation [11], and tested by germline chimeras in pigs.…”

Section: Introductionmentioning

confidence: 99%

Telomere Reprogramming and Maintenance in Porcine iPS Cells

Ruan

Liu

et al. 2013

PLoS ONE

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Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.

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Section: Introductionmentioning

confidence: 99%

Telomere Reprogramming and Maintenance in Porcine iPS Cells

Ruan

Liu

et al. 2013

PLoS ONE

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“…As Dr. E. Cozzi explained in his talk, significant advances have been achieved in the understanding of the immunological responses leading to xenograft rejection [25] and approaches are being pursued to overcome the obstacles to the long-term survival of xenografts (pharmacological immunosuppression, tolerance inducing regimens in the absence of immunosuppression, accommodation despite xenoreactive antibodies, and complement and genetic engineering of the donor source, to render the xenograft greater immunological compatibility).…”

Section: Onementioning

confidence: 99%

General Overview of the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations

Vázquez-Álvarez

Sanz‐Ruiz

Gutiérrez

et al. 2009

J. of Cardiovasc. Trans. Res.

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Being one of the main stem cell therapy meetings of the year, the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held on April 23rd-24th, 2009, at the Auditorium of the High Council of Scientific Research of Spain (CSIC) in Madrid. Gathering the most prestigious basic researchers and clinical experts in the field of cardiovascular regenerative medicine, the aim of the meeting was to discuss the available evidence and the recent contributions from preclinical investigators, cardiologists, and cardiac surgeons in a participative translational fashion. The role of young "clinician scientists" was reinforced with a special poster session and three awards. The main conclusions of the symposium were (1) that standardization, larger clinical trials, and true translational research are needed, and (2) that new-allogeneic-stem cell products, biotechnological devices, and cell-based bioartificial organs are potentially exciting options for the future.

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“…Pigs are one of the preferred choices for xenotransplantation because of anatomical and physiological similarities to humans, relatively short generation time, and ease of production of transgenic pigs (Cozzi et al 2009;Gola and Mazurek 2014). The phylogenetic distance between pigs and humans reduces the risk of transmission of viral infections, with screening and qualified breeding further lowering the risk of other zoonotic infections (Gola and Mazurek 2014).…”

Section: Because Cases Of Xenographic Transmission Of Infectious Disementioning

confidence: 99%

Preliminary PCR-Based Screening Indicates a Higher Incidence of Porcine Endogenous Retrovirus Subtype C (PERV-C) in Feral Versus Domestic Swine

Acharya

Wallis

Keener

et al. 2019

Transactions of the Kansas Academy of Science

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Xenotransplantation is considered a potential alternative to allotransplantation to relieve the current shortage of human organs. Due to their similar size and physiology, the organs of pigs are of particular interest for this purpose. Endogenous retroviruses are a result of integration of retroviral genomes into the genome of infected germ cells as DNA proviruses, which are then carried in all cells of the offspring of the organism. Porcine endogenous retroviruses (PERVs) are of special concern because they are found in pig organs and tissues that might otherwise be used for xenotransplantation. PERV proviruses can be induced to replicate and recombine in pigs, and have been shown to infect human cells in vitro. There are three subtypes of PERVs based on differences in the receptor binding domain of the env protein; PERV-A, PERV-B, and PERV-C. PERVs A and B can infect human cells in vitro and can recombine with PERV-C, resulting in a recombinant virus with a higher rate of replication in pig and human cell lines. In this study, we used a PCR-based analysis of 50 domestic and 35 feral pigs to study the distribution of PERVs A, B, and C in swine raised under domestic conditions, versus feral swine from rural areas. PERV-A and PERV-B were universal in both domestic and feral swine. Feral swine had a higher incidence of PERV-C (85.7%) compared to domestic swine (42.0%). Further studies in other feral swine herds are ongoing to verify this observation.

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Xenotransplantation as a model of integrated, multidisciplinary research

Cited by 20 publications

References 92 publications

Telomere Reprogramming and Maintenance in Porcine iPS Cells

Telomere Reprogramming and Maintenance in Porcine iPS Cells

General Overview of the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations

Preliminary PCR-Based Screening Indicates a Higher Incidence of Porcine Endogenous Retrovirus Subtype C (PERV-C) in Feral Versus Domestic Swine

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