[Living donation liver transplantation in children]. / Lebendspende-Lebertransplantation beim Kind.

Liver transplantation is the first-line therapy for children with acute and chronic hepatic failure, metabolic liver diseases and liver tumors. As most of the children with end-stage liver disease are very small in stature the resources of compatible organs of deceased donors are limited. Living liver donation was able to nearly eliminate waiting list mortality with excellent patient and graft survival. As 80% of the pediatric recipients have a body weight <25 kg donation of the left lateral lobe (segments II+III) is sufficient in most of the cases. According to a standardization of the surgical procedures as well as the preoperative, intraoperative and postoperative management donation of the left lateral lobe advanced to a procedure with very low donor morbidity and mortality rates. The complexity of hepatic disease patterns in pediatric patients which often affect other organ systems demand a close cooperation with an experienced pediatric team. Pediatric living donor liver transplantation requires high expertise in liver surgery and split liver transplantation and should therefore only be performed in transplant centers meeting these high qualifications.

Multipotent cells of monocytic origin improve damaged heart function.

Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.

Different in vivo tolerogenicity of MHC class I peptides.

The efficacy of MHC class I-derived peptides to induce tolerance was tested in a cardiac transplantation model. Two 25-mer peptides from the polymorphic region of the DA class I molecule (RT1.Aa) were synthesized by F-moc chemistry and injected intrathymically or intraperitoneally into LEW (RT1.1) responder animals. Intrathymic treatment of the recipient animals with peptide 1 (residues 56-80) accompanied by intraperitoneal treatment with peptide 4 (residues 96-120) led to indefinite survival of allogeneic DA cardiac allografts (n = 7; > 100 days). The tolerogenicity of both peptides differed according to the site of inoculation, as donor-specific tolerance was only observed after administration of peptide 1 into the thymus and injection of peptide 2 into the abdominal cavity of LEW recipients, but not vice versa. Donor-specific tolerance was confirmed in vivo by grafting of full-thickness skin and in vitro by appropriate proliferation and cytotoxicity assays using donor and third-party rats. Donor-specific tolerance was associated with up-regulation of interleukin-4, transforming growth factor beta, and interleukin-10 gene expression within cardiac allografts, thus suggesting intrathymic clonal deletion and external suppression with expansion of T-helper 2-type lymphocytes as the underlying mechanisms of tolerance induction.

[Significance of allopeptide-induced expression of Fas ligand (FasL) in parenchyma of allogenic heart transplants as the cause of donor-specific tolerance induction]. / Die Bedeutung der Allopeptid-induzierten Expression von Fas-Ligand (FasL) im Parenchym allogener Herztransplantate als Ursache der spenderspezifischen Toleranzinduktion.

This study proves the tolerogenicity of polymorphic allopeptides. Combined administration of peptides derived from the alpha 1 (intrathymal) and the alpha 2 (intraperitoneal) helical region of the donor RT1.A(a) molecule induced specific tolerance in a rat model of cardiac allotransplantation. The underlying tolerance mechanism was mediated by selective depletion of alloreactive T cells within the thymus and Fas-L-induced apoptosis within the graft.