scholarly journals Remaining Physiological Barriers in Porcine Kidney Xenotransplantation: Potential Pathways behind Proteinuria as well as Factors Related to Growth Discrepancies following Pig-to-Kidney Xenotransplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Jigesh A. Shah ◽  
Miguel A. Lanaspa ◽  
Tatsu Tanabe ◽  
Hironosuke Watanabe ◽  
Richard J. Johnson ◽  
...  

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis.

2020 ◽  
Vol 21 (18) ◽  
pp. 6468
Author(s):  
Annika Mohr ◽  
Jens G. Brockmann ◽  
Felix Becker

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.


2021 ◽  
Vol 2 (4) ◽  
pp. 412-424
Author(s):  
Nadine Wenzel ◽  
Rainer Blasczyk ◽  
Constanca Figueiredo

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Abraham J. Matar ◽  
Rebecca L. Crepeau ◽  
Gerhard S. Mundinger ◽  
Curtis L. Cetrulo ◽  
Radbeh Torabi

Over the past twenty years, significant technical strides have been made in the area of vascularized composite tissue allotransplantation (VCA). As in solid organ transplantation, the allogeneic immune response remains a significant barrier to long-term VCA survival and function. Strategies to overcome acute and chronic rejection, minimize immunosuppression and prolong VCA survival have important clinical implications. Historically, large animals have provided a valuable model for testing the clinical translatability of immune modulating approaches in transplantation, including tolerance induction, co-stimulation blockade, cellular therapies, and ex vivo perfusion. Recently, significant advancements have been made in these arenas utilizing large animal VCA models. In this comprehensive review, we highlight recent immune strategies undertaken to improve VCA outcomes with a focus on relevant preclinical large animal models.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5325-5325
Author(s):  
Mohamad A. Younes ◽  
Jonathan D Perez ◽  
Zaid Alirhayim ◽  
Cesar Ochoa ◽  
Ruchir Patel ◽  
...  

Abstract The risk of transformation of MGUS to MM is well studied and considered to be around 1%/year. However, this risk is not well defined in patients who undergo solid organ transplantation. A study by Jimenez et al Transplantation,2011 Sep 15;92(5):570-4 found no increased risk of transformation of MGUS to MM, but the sample size of patients who were diagnosed with MGUS prior to transplantation was small (34 patients). In another study by Naina et al Am J Nephrol. 2012;35(4):365-71, 2 out of 17 (11.7%) patients with pre-transplant MGUS and kidney transplant developed smoldering MM. To investigate this topic further, we reviewed the charts of patients who underwent solid organ transplant and who had a pre-transplant diagnosis of MGUS between years 2000 and 2010 and studied the incidence of transformation to MM in these patients. Patients who had MGUS diagnosed after the solid organ transplant were excluded. 57 patients were eligible. The number of patients with different kinds of transplant was as follows: 22 had liver transplant, 31 had kidney transplant, 3 patients had lung transplant, and 1 patient had heart transplant. The mean age was 57.3 years (range 32-76 years). 26.3% were females. The mean follow up was 45.6 months (range 1-156 months). The mean M protein on diagnosis was 0.52 g/dl. 16 patients had pre-transplant bone marrow biopsy with a mean plasma cell percentage of 4% (range 1-9%). 14 patients had normal cytogenetics and 1 patient had Trisomy 11 and another had deletion Y. 29 patients had their serum light chain ratio checked and it was normal in 22 out of 29 patients and abnormal in 7 patients. None of the 57 patients were diagnosed with MM during the follow up period. 1 patient developed PTLD 5 years post transplant. 14 patients died and 43 patients were still alive at the time of last follow up. Follow up on M protein was available for 35 patients with a mean follow up of 54 months (range 2-144 months) with the following observations: 19 patients (54%) had stable M protein (10 kidney, 8 liver, 1 lung), 6 patients (17%) had increase in M protein by at least 0.1 g/dl (4 kidney and 2 liver), and 10 patients had their M protein decrease or resolve (5 kidney, 4 liver, 1 Heart). Mean time to death was 18.65 months (1- 68.8 months). None of the deaths were related to MM and the causes were as follows: infection (3), GI bleed (1), malignancy (3) being Kaposi sarcoma, HCC and PTLD, liver failure (2), uremia (1), CVA (1), unknown (3). Immunosuppressants included mainly medrol, prograf, cellcept, cyclosporine and rapamune. Conclusion MGUS is not a contraindication to solid organ transplant as none of the patient developed MM during the follow up period and deaths were not related to progression of MGUS to MM. As 6 out of 57 patients (10.5%) had increase in M protein despite none being diagnosed with MM, we do suggest continued follow up on these patients at least once a year. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Yanhong Ma ◽  
...  

AbstractOrgan preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.


2021 ◽  
Vol 10 (17) ◽  
pp. 3838
Author(s):  
Margot Fodor ◽  
Julia Hofmann ◽  
Lukas Lanser ◽  
Giorgi Otarashvili ◽  
Marlene Pühringer ◽  
...  

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation.


2018 ◽  
Vol 19 (11) ◽  
pp. 3509 ◽  
Author(s):  
Philipp Stiegler ◽  
Augustinas Bausys ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Peter Schemmer

Solid organ transplantation is the “gold standard” for patients with end-stage organ disease. However, the supply of donor organs is critical, with an increased organ shortage over the last few years resulting in a significant mortality of patients on waiting lists. New strategies to overcome the shortage of organs are urgently needed. Some experimental studies focus on melatonin to improve the donor pool and to protect the graft; however, current research has not reached the clinical level. Therefore, this review provides a comprehensive overview of the data available, indicating that clinical evaluation is warranted.


2017 ◽  
Vol 36 (5) ◽  
pp. 445-448 ◽  
Author(s):  
Jennifer L. Lee ◽  
Cyd K. Eaton ◽  
Kristin Loiselle Rich ◽  
Bonney Reed-Knight ◽  
Rochelle S. Liverman ◽  
...  

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