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State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation

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A special issue of Transplantology (ISSN 2673-3943). This special issue belongs to the section "Artificial Organs, Stem Cells and Xenotransplantation".

Deadline for manuscript submissions: closed (20 July 2022) | Viewed by 17758

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Special Issue Editor

Prof. Dr. Constança Figueiredo

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Guest Editor

Institute for Transfusion Medicine and Transplant Engineering, Carl‐Neuberg‐Strasse 1, D‐30625 Hannover, Germany
Interests: transplantation; cell and gene therapy; immunology; histocompatibility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Transplantation often remains the only therapeutic option for end-stage organ failure. However, the shortage of the donor pool, significant transplant rejection rates, and severe side effects of immunosuppression indicate the urgent need for the development of strategies to support graft survival after transplantation and decrease the necessity for strong immunosuppressive regimens. Recently, different interdisciplinary approaches and biotechnological developments have been designed to increase donor pools, improve organ quality, and support graft survival after allogeneic and xenogeneic transplantation. Progresses in the fields of ex vivo organ perfusion alone or in combination with immunomodulatory strategies using gene or cell therapy methods have shown promising results in reconditioning and regenerating organs as well as supporting graft survival. In addition, the protective effect of specific proteins and molecules against ischemia reperfusion injury has been demonstrated. New regulatory mechanisms and gene candidates have been identified as potential targets for the development of innovative therapies to prevent graft failure. In particular, remarkable advances have been made in the field of xenotransplantation such as in the generation of new transgenic animals or development of novel strategies to promote biosafety.

This Special Issue combines comprehensive reviews and cutting-edge basic, translational, and clinical reports addressing innovative strategies to modify tissues or organs to support graft function and survival after allogeneic and xenogeneic transplantation.

Prof. Dr. Constança Figueiredo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Transplantology is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Transplantation
Xenotransplantation
Organ conditioning
Cell Therapy
Gene Therapy
Gene regulation
Gene editing
Ex vivo Perfusion
Fibrosis

Published Papers (5 papers)

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Research

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8 pages, 801 KiB

Open AccessArticle

AmnioClip-Plus as Sutureless Alternative to Amniotic Membrane Transplantation to Improve Healing of Ocular Surface Disorders

by Nicola Hofmann, Anna-Katharina Salz, Kristin Kleinhoff, Niklas Möhle, Martin Börgel, Nancy Diedenhofen and Katrin Engelmann

Transplantology 2021, 2(4), 425-432; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2040040 - 18 Oct 2021

Cited by 3 | Viewed by 2264

Abstract

The medicinal benefits of amniotic membrane transplantation for ocular surface disorders are well accepted worldwide. Even in high-risk keratoplasties, the concomitant use of amniotic membrane has demonstrated its value in improving graft survival. However, its seam-associated application can lead to an additional trauma. The AmnioClip ring system, into which the amniotic membrane is clamped (AmnioClip-plus, AC+), was developed to avoid this surgical intervention. The AC+ is placed on the cornea, similar to a contact lens, under local anesthesia and can therefore be applied repeatedly. Clinical practice demonstrates the easy handling, good compatibility, and efficacy of this minimally invasive method. Full article

(This article belongs to the Special Issue State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation)

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11 pages, 1413 KiB

Open AccessFeature PaperArticle

The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys

by L. Annick van Furth, Leonie H. Venema, Koen D. W. Hendriks, Pieter C. Vogelaar, Guido Krenning and Henri G. D. Leuvenink

Transplantology 2021, 2(3), 304-314; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2030031 - 23 Aug 2021

Cited by 2 | Viewed by 2877

Abstract

Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function. Full article

(This article belongs to the Special Issue State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation)

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Review

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13 pages, 299 KiB

Open AccessReview

Animal Models in Allogenic Solid Organ Transplantation

by Nadine Wenzel, Rainer Blasczyk and Constanca Figueiredo

Transplantology 2021, 2(4), 412-424; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2040039 - 03 Oct 2021

Cited by 5 | Viewed by 4741

Abstract

Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research. Full article

(This article belongs to the Special Issue State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation)

15 pages, 1369 KiB

Open AccessReview

Donor-Derived Cell-Free DNA to Diagnose Graft Rejection Post-Transplant: Past, Present and Future

by Naveen Kumar, Rashmi Rana, Devender Singh Rana, Anurag Gupta and Mohinder Pal Sachdeva

Transplantology 2021, 2(3), 348-361; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2030034 - 10 Sep 2021

Cited by 4 | Viewed by 3662

Abstract

Donor-derived cell-free DNA (dd-cfDNA) is a non-invasive biomarker that is more sensitive and specific towards diagnosing any graft injury or rejection. Due to its applicability over all transplanted organs irrespective of age, sex, race, ethnicity, and the non-requirement of a donor sample, it emerges as a new gold standard for graft health and rejection monitoring. Published research articles describing the role and efficiency of dd-cfDNA were identified and scrutinized to acquire a brief understanding of the history, evolution, emergence, role, efficiency, and applicability of dd-cfDNA in the field of transplantation. The dd-cfDNA can be quantified using quantitative PCR, next-generation sequencing, and droplet digital PCR, and there is a commendatory outcome in terms of diagnosing graft injury and monitoring graft health. The increased levels of dd-cfDNA can diagnose the rejection prior to any other presently used biochemistry or immunological assay methods. Biopsies are performed when these tests show any signs of injury and/or rejection. Therefore, by the time these tests predict and show any unusual or improper activity of the graft, the graft is already damaged by almost 50%. This review elucidates the evolution, physiology, techniques, limitations, and prospects of dd-cfDNA as a biomarker for post-transplant graft damage and rejection. Full article

(This article belongs to the Special Issue State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation)

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13 pages, 3361 KiB

Open AccessFeature PaperReview

Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation?

by Rebecca Panconesi, Mauricio Flores Carvalho, Matteo Mueller, Philipp Dutkowski, Paolo Muiesan and Andrea Schlegel

Transplantology 2021, 2(2), 149-161; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2020015 - 12 May 2021

Cited by 11 | Viewed by 3027

Abstract

Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed. Full article

(This article belongs to the Special Issue State-of-the-Art of Engineering and Regenerating Organs to Improve Graft Survival after Transplantation)

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