Publications by authors named "Leo Buhler"

This report summarizes the content of a debate sponsored by eGenesis Bio, organized by the International Xenotransplantation Association (IXA), and attended by more than 150 delegates in the context of the IPITA-IXA-CTRMS Joint Congress held in San Diego in October 2023. The debate centered around two important immunological topics relating to xenotransplantation. The first was a debate relating to the statement that "HLA-sensitized patients are at higher risk for rejecting a pig xenograft.

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Article Synopsis
  • Platelets are important for liver regeneration, and this study focused on how Transforming Growth Factor Beta 1 (TGFβ1) from platelets impacts this process after liver surgery.
  • The researchers used two types of mice: those lacking platelet-derived TGFβ1 and normal mice, measuring various factors related to liver regeneration and platelet behavior post-surgery.
  • Findings revealed that the absence of TGFβ1 led to lower liver cell growth (hepatocyte proliferation) and disrupted levels of other growth factors, underscoring TGFβ1's role in liver regeneration and platelet stability.
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Background: In rodents, hydrogen sulfide (HS) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of HS are conserved in pigs, a more clinically relevant model.

Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion.

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A conference on progress in the development of xenotransplantation in China was held in Neijiang, Sichuan, in May 2023, and was attended by approximately 100 established researchers and trainees. Progress in xenotransplantation research was reviewed by both Chinese and foreign experts. The topics discussed ranged from genetic engineering of pigs and the results of pig-to-nonhuman primate organ transplantation to the requirements for designated pathogen-free (DPF) pig facilities and regulation of xenotransplantation.

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Background: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis.

Methods: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit.

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Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions.

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Based on a case report, this review explores the genomic landscape for patients with liposarcomas and possible relationships with gene mutations related to craniosynostosis. We describe the case of a 40-year-old man, known for a surgical correction of craniosynostosis before the age of 1 year, who underwent a radical resection of a voluminous retroperitoneal liposarcoma; histopathological analysis revealed a low-grade well-differentiated, mostly sclerosing, liposarcoma. A genetic analysis searching for mutations in blood DNA was performed and did not detect any specific mutation.

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Objective: Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application.

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The diagnosis of intra-abdominal infection and post-operative peritonitis based on clinical examination, biomarkers and radiological signs, should be made as early as possible to improve outcomes and decrease mortality through early and optimal source control, adequate surgery and appropriate antibiotic therapy (Montravers . Therapeutic management of peritonitis: a comprehensive guide for intensivists. 2016;:1234-47).

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Unlabelled: The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury.

Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia.

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Background: Utilization of autologous stem cells has been proposed for the treatment of anal incontinence despite a lack of understanding of their mechanism of action and of the physiological healing process of anal sphincters after injury.

Aims: We aim to develop a technique allowing isolation and further study of local mesenchymal stem cells, directly from anal canal transition zone in pig.

Methods: Anal canal was resected "en bloc" from two young pigs and further microdissected.

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Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft.

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Diabetes is a metabolic disease characterized by insulin deficiency. Bioengineering of stem cells with the aim to restore insulin production and glucose regulation has the potential to cure diabetic patients. In this review, we focus on the recent developments for bioengineering of induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and pancreatic progenitor cells in view of generating insulin producing and glucose regulating cells for β-cell replacement therapies.

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To obtain meaningful results of hepatic stellate cell (HSC) function, it is crucial to use highly pure HSC populations. Our aim was to optimize HSC isolation from mice livers without exploiting the characteristically transient vitamin A autofluorescence of HSC. HSCs were isolated from C57BL/6 mice using a two-step collagenase digestion and Nycodenz gradient separation followed by CD11b-negative sorting step in order to remove contaminating macrophages and dendritic cells.

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Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression.

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Robot-assisted donor nephrectomy (RDN) is increasingly used due to its advantages such as its precision and reduced learning curve when compared to laparoscopic techniques. Concerns remain among surgeons regarding possible longer warm ischemia time. This study aimed to compare patients undergoing robotic living donor nephrectomy to the more frequently used hand-assisted laparoscopic nephrectomy (HLDN) technique, focusing on warm ischemia time, total operative time, learning curve, hospital length of stay, donor renal function and post-operative complications.

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Type 1 diabetes (T1D) is a widespread disease, affecting approximately 41.5 million people worldwide. It is generally treated with exogenous insulin, maintaining physiological blood glucose levels but also leading to long-term therapeutic complications.

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Background: Following the recommendations by a panel of experts gathered by the World Health Organization in 2005, an inventory was established to collect practices of human xenotransplantation worldwide ( www.humanxenotransplant.org ).

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CD160 is a member of the immunoglobulin superfamily with a pattern of expression mainly restricted to cytotoxic cells. To assess the functional relevance of the HVEM/CD160 signaling pathway in allogeneic cytotoxic responses, exon 2 of the CD160 gene was targeted by CRISPR/Cas9 to generate CD160 deficient mice. Next, we evaluated the impact of CD160 deficiency in the course of an alloreactive response.

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