Transplantable liver production plan

Hata, Toshiyuki; Üemoto, Shinji; Kobayashi, Eiji

doi:10.4161/org.25760

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…Several strategies have been investigated to optimize IS after LT in order to achieve a IS-free status, including: (I) development of target IS regimens (i.e., antibodies or fusion proteins direct against molecules involved in T cell activation or targeting specific immune cell subsets) (49); (II) development of biomarkers to minimize IS (anti-HLA antibodies, non-invasive transcriptional or serological markers of rejection) (50,51); (III) induction of tolerance [e.g., induction of donor-type hematopoietic chimerism in living donor liver transplantation (LDLT)] (52); (IV) modulation of the liver allograft immunogenicity by the use of ex vivo machine perfusion of the liver grafts to modulate inflammatory response (53); (V) generation of bioengineered liver grafts by using acellular liver scaffolds repopulated with patient derived cells (54,55).…”

Section: Current Prospects and Future Perspectivesmentioning

confidence: 99%

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Angelico

Parente

Manzia

2017

Transl. Gastroenterol. Hepatol.

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Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 15-20%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients.

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Section: Current Prospects and Future Perspectivesmentioning

confidence: 99%

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Angelico

Parente

Manzia

2017

Transl. Gastroenterol. Hepatol.

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“…Attempts are also made at reducing the impact of livestock products on human health and the environment [ 10 , 11 ]. In medical research, gene editing of farm animals can be used in a wide range of applications, from large-scale protein expression to the creation of humanized organs for transplantation (xenografts) [ 12 , 13 , 14 ]. Some large animals can be successfully used as preclinical models in testing drugs, artificial implants or surgical procedures [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Perspectives in Genome-Editing Techniques for Livestock

Popova

Bets

Kozhevnikova

2023

Animals

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Genome editing of farm animals has undeniable practical applications. It helps to improve production traits, enhances the economic value of livestock, and increases disease resistance. Gene-modified animals are also used for biomedical research and drug production and demonstrate the potential to be used as xenograft donors for humans. The recent discovery of site-specific nucleases that allow precision genome editing of a single-cell embryo (or embryonic stem cells) and the development of new embryological delivery manipulations have revolutionized the transgenesis field. These relatively new approaches have already proven to be efficient and reliable for genome engineering and have wide potential for use in agriculture. A number of advanced methodologies have been tested in laboratory models and might be considered for application in livestock animals. At the same time, these methods must meet the requirements of safety, efficiency and availability of their application for a wide range of farm animals. This review aims at covering a brief history of livestock animal genome engineering and outlines possible future directions to design optimal and cost-effective tools for transgenesis in farm species.

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“…A clear early example of this is the cystic fibrosis transmembrane conductance regulator ( CFTR ) knockout pig, which is far more clinically similar to humans than a CFTR knockout in mice [2]. Gene editing in large animals also has the potential to aid human medicine directly, from creation of humanized protein drugs [3] to creation of humanized transplant organs (xenografts) [4, 5]. …”

Section: Introductionmentioning

confidence: 99%

Genome Editing in Large Animals

West

Gill

2016

Journal of Equine Veterinary Science

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Genome editing in large animals has tremendous practical applications, from more accurate models for medical research through improved animal welfare and production efficiency. Although genetic modification in large animals has a 30 year history, until recently technical issues limited its utility. The original methods – pronuclear injection and integrating viruses – were plagued with problems associated with low efficiency, silencing, poor regulation of gene expression, and variability associated with random integration. With the advent of site specific nucleases such as TALEN and CRISPR/Cas9, precision editing became possible. When used on their own, these can be used to truncate or knockout genes through non-homologous end joining (NHEJ) with relatively high efficiency. When used with a template containing desired gene edits, these can be used to allow insertion of any desired changes to the genome through homologous recombination (HR) with substantially lower efficiency. Consideration must be given to the issues of marker sets and off-target effects. Somatic cell nuclear transfer is most commonly used to create animals from gene edited cells, but direct zygote injection and use of spermatogonial stem cells are alternatives under development. In developing gene editing projects, priority must be given to understanding the potential for off-target or unexpected effects of planned edits, which have been common in the past. Because of the increasing technical sophistication with which it can be accomplished, genome editing is poised to revolutionize large animal genetics, but attention must be paid to the underlying biology in order to maximize benefit.

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Transplantable liver production plan

Cited by 9 publications

References 25 publications

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Perspectives in Genome-Editing Techniques for Livestock

Genome Editing in Large Animals

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