A5017993985- Organ Transplantation Techniques and Outcomes
- Xenotransplantation and immune response
- Renal Transplantation Outcomes and Treatments
- Pancreatic function and diabetes
- Hematopoietic Stem Cell Transplantation
- Tissue Engineering and Regenerative Medicine
- Liver physiology and pathology
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Liver Disease Diagnosis and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Liver Diseases and Immunity
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Clinical Nutrition and Gastroenterology
- Pregnancy and preeclampsia studies
- Signaling Pathways in Disease
- Pregnancy and Medication Impact
- Biomedical Ethics and Regulation
- Biochemical and Molecular Research
- Polyomavirus and related diseases
- Complement system in diseases
- Multiple Sclerosis Research Studies
- Mesenchymal stem cell research
Karolinska Institutet
2017-2025
Massachusetts General Hospital
2022-2025
Harvard University
2023-2025
Karolinska University Hospital
2015-2022
Abstract Recent human decedent model studies 1,2 and compassionate xenograft use 3 have explored the promise of porcine organs for transplantation. To proceed to studies, a clinically ready donor must be engineered its successfully tested in nonhuman primates. Here we describe design, creation long-term life-supporting function kidney grafts from genetically transplanted into cynomolgus monkey model. The was carry 69 genomic edits, eliminating glycan antigens, overexpressing transgenes...
Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received gene-edited porcine kidney 69 genomic edits, including deletion of three glycan antigens, inactivation endogenous retroviruses, insertion seven human transgenes. The xenograft functioned immediately. patient's creatinine levels decreased promptly progressively, dialysis was no...
Clinical hepatocyte transplantation is hampered by low engraftment rates and gradual loss of function resulting in incomplete correction the underlying disease. Preconditioning with partial hepatectomy improves animal studies. Our aim was to study safety efficacy preconditioning clinical transplantation. Two patients Crigler-Najjar syndrome type I underwent liver resection followed A transient increase growth factor seen, suggesting that this procedure provides a regenerative stimulus. Serum...
Abstract Alpha 1-antitrypsin (AAT) deficiency arises from an inherited mutation in the SERPINA1 gene. The disease causes damage liver where majority of AAT protein is produced. Lack functioning circulating also uninhibited elastolytic activity lungs leading to deficiency-related emphysema. only therapy apart transplantation augmentation with human pooled sera, which reserved for patients advanced lung caused by severe deficiency. We tested modified mRNA encoding primary hepatocytes culture,...
Abstract Antibody‐mediated rejection (AMR) is a common cause of graft failure after pig‐to‐nonhuman primate organ transplantation, even when the from pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases kidney transplantation into immunosuppressed baboons in which we identify novel associated initiation AMR. In first, membranous nephropathy was initiating factor then apparent loss therapeutic anti‐CD154 monoclonal antibody...
<title>Abstract</title> Genetically modified pigs are being developed to address the critical shortage of human organs for transplantation. We have previously demonstrated significantly prolonged survival porcine xenografts devoid three major carbohydrate xenoantigens (3KO) by incorporating transgenes (HTGs). However, optimal HTG combination and mechanisms underlying improved xenograft following such genetic editing remain undefined. In current study, we evaluated, in nonhuman primates,...
Hematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic (HSC) engraftment, it appears essential to establish niches for the HSCs by depleting host HSCs. date, this been achievable only...
Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), known to recur after LT. Since the recurrence of NASH can lead graft failure, identification predictive factors needed preventive strategies should be implemented.We retrospectively examined 95 patients who had undergone LT or alcoholic disease (ALD) as primary indication. We evaluated peritransplant characteristics histological findings 1-year post among transplant due ALD.Pre-LT...
The main goal of the therapy with purified human plasma alpha1-antitrypsin (A1AT) is to increase A1AT levels and prevent lungs from elastolytic activity in patients PiZZ (Glu342Lys) deficiency-related emphysema. Potential hepatic gains this are unknown. Herein, we investigated effect on SERPINA1 (gene encoding A1AT) expression. expression was determined or plus Oncostatin M (OSM) treated primary hepatocytes isolated liver tissues deficient control tissues. In addition, mRNA assessed lung...
A liver-humanized mouse model for CPS1-deficiency was generated by the high-level repopulation of liver with CPS1-deficient human hepatocytes. When compared mice that are highly repopulated CPS1-proficient hepatocytes, hepatocytes exhibited characteristic symptoms CPS1 deficiency including an 80% reduction in metabolic activity, delayed clearance ammonium chloride infusion, elevated glutamine and glutamate levels, impaired metabolism [15 N]ammonium into urea, no other obvious phenotypic...
Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic diseases, but progress has been hampered by scarcity of available organs. Here, hepatocytes isolated from livers procured neonatal hepatocyte donation program within research setting were assessed function suitability transplantation. Organ was considered infants who died in intensive care the Stockholm region during 2015–2021. Inclusion when decision to discontinue life-sustaining had made hepatectomy...
ABSTRACT Transplantation remains the preferred treatment for end‐stage kidney disease but is critically limited by number of available organs. Xenografts from genetically modified pigs have become a promising solution to loss life while waiting transplantation. However, current clinical model xenotransplantation will require off‐site procurement, leading period ischemia during transportation. As today, there understanding regarding preservation these organs, including duration viability, and...
Explanted livers from patients with familial amyloid polyneuropathy have often been used for domino liver transplantation (DLT). This has expanded the organ pool transplantation. We evaluated effects of a single-center DLT program on waiting list duration and patient survival. Liver transplants conducted 2007 to 2017 were analyzed. Selected patients, all transplant candidates above age 60 years hepatocellular carcinoma, offered DLT. Survival, time list, operative factors evaluated. The study...
Belatacept is currently an only FDA approved costimulatory blockade (CB) used as alternative to calcineurin inhibitors in kidney transplantation. However, it has been associated with higher rates of acute cellular rejection (ACR) and more effective CB sought. Blockade the CD154/CD40 pathway anti-CD154 antibody (aCD154) shown be inhibiting alloimmune responses than CTLA4Ig. Unfortunately, clinical application aCD154 abandoned due its thrombophilic property which appears mediated by FcγRIIA...
Introduction: Xenotransplantation holds immense potential as replacement therapy for end-stage renal disease and a solution to the global organ shortage. Development of porcine xenografts with triple knockouts (3KO) known xenoantigens (GGTA1, CMAH, B4GALNT2) have partly mitigated hyperacute rejection by natural antibodies unmodified organs1. Transgenic expression human transgenes has further considerably improved xenograft survival overcoming molecular incompatibilities between pigs humans2....