ArticlesTransplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study
Introduction
Extrahepatic portal vein obstruction leads to impaired hepatopedal blood flow from the superior mesenteric vein, splenic vein, and coronary veins through the portal vein. The disorder is by definition not associated with intrinsic liver disease, and can be congenital or acquired.1, 2 Its pathogenesis in children is unexplained. Various factors such as hereditary thrombophilias, neonatal abdominal surgery, sepsis, umbilical vein catheterisation, and dehydration are known to predispose development of extrahepatic portal vein obstruction. The initial clinical manifestation is characterised either by episodes of upper gastrointestinal bleeding or by splenomegaly on routine clinical examination. The disorder can result in complications such as variceal haemorrhage, enlarged spleen, biliopathy, or developmental retardation, and neurocognitive disability.3 Upper gastrointestinal bleeding in children and adults with extrahepatic portal vein obstruction can even be asymptomatic and results in high mortality and morbidity. Almost 80% of children diagnosed with the disorder will have at least one episode of such bleeding in their lifetime.2 Episodes are characterised by high morbidity, including frequent hospital admissions, an increase in school absenteeism, and emotional stress for the children and their families. Thus, appropriate diagnosis and treatment are needed to reduce morbidity and mortality. Diagnosis is made by abdominal Doppler ultrasonography and CT angiography. Surgical guidelines recommend restoration of the portal blood flow by use of autologous veins for bypass between the superior mesenteric vein and the left intrahepatic portal vein, which is known as the meso Rex bypass.1
Use of umbilical veins for the bypass has produced varied results.4, 5 When this technique is not adequate, other vessels such as the internal jugular veins or even the internal iliac, splenic, inferior mesenteric, or saphenous veins can be used. The recommended technique is the use of the internal jugular vein.1 Other attempts, including use of artificial grafts and cryopreserved veins, have shortcomings and are associated with little success.1, 6, 7 The ideal solution would be to use an autologous vein to repair the damage,1 which would avoid dependence on artificial grafts or allografts.
If the meso Rex procedure fails, patients are often referred back for palliative treatment, with the aforementioned risks, or—if lifethreatening complications occur—are referred for liver transplantation, which sometimes includes a portocaval hemitransposition8 or a multivisceral organ transplantation.9 These procedures lead to a need for lifelong treatment with immunosuppressive drugs and have a high rate of morbidity and mortality due to the treatment itself.
We report a meso Rex procedure that aimed to address the aforementioned issues by using a decellularised donor vein, recellularised with autologous stem cells.
Section snippets
Patient
A 1-year-old girl developed thrombocytopenia and splenomegaly and was diagnosed with idiopathic thrombocytopenic purpura and followed up for several years at a local hospital. When the patient was 9·5 years old she was reassessed and was referred to the Sahlgrenska University Hospital in Gothenburg, Sweden. Oesophageal varicose veins and splenomegaly were confirmed. The patient's international normalised ratio was slightly elevated (1·4), concentrations of protein S and protein C were normal,
Results
Histological analysis of the first vein graft showed it was successfully decellularised after seven cycles of decellularisation. Figure 3 shows the gross morphology and histology of the iliac vein used in the first transplantation before and after decellularisation. The architecture of the decellularised vein was different from the native control. We noted no nuclei or expression of HLA class I or II antigens on the decellularised vein graft at the end of cycle seven and no anti-endothelial
Discussion
We show that recellularisation of a decellularised human iliac vein with autologous stem cells is possible, and subsequent use in a bypass procedure can result in good blood flow rates and normal laboratory test values. A previous study in a sheep model showed that endothelial cell coverage is a prerequisite for successful patency and function of vein valves.11 The investigators of that study noted a significant reduction of thrombogenicity in the decellularised vein as a result of
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