Hintergrund: Die systemische Mastozytose als klonale Erkrankung der hämatopoetischen Stammzelle ist eine seltene Erkrankung und stellt aufgrund der Heterogenität des klinischen Bildes eine diagnostische Herausforderung dar. Die Therapie richtet sich häufig nach der vorherrschenden Symptomatik und nur für wenige therapeutische Optionen besteht eine gesicherte Evidenz.
Oval cells, small cells with oval-shaped nuclei, are induced to proliferate in the livers of animals treated with carcinogens and are thought to be related to liver stem cells and/or committed liver progenitor cell populations. We have developed protocols for identifying and isolating antigenically related cell populations present in normal tissues using monoclonal antibodies to oval cell antigens and fluorescence-activated cell sorting. We have isolated oval cell-antigen-positive (OCAP) cells from embryonic, neonatal, and adult rat livers and have identified culture conditions permitting their growth in culture., , The requirements for growth of the OCAP cells included substrata of type IV collagen mixed with laminin, basal medium with complex lipids and low calcium, specific growth factors (most potently, insulin-like growth factor II and granulocyte-macrophage colony-stimulating factor), and co-cultures of embryonic, liver-specific stroma, strongly suggesting paracrine signaling between hepatic and hemopoietic precursor cells., , The growing OCAP cultures proved to be uniformly expressing oval cell markers but were nevertheless a mixture of hepatic and hemopoietic precursor cells. To separate the hepatic and hemopoietic subpopulations of OCAP cells, we surveyed known antibodies and found ones that uniquely identify either hepatic or hemopoietic cells. Several of these antibodies were used in panning procedures and fluorescence-activated cell sorting to eliminate contaminant cell populations, particularly hemopoietic and endothelial cells. Using specific flow cytometric parameters, three cellular subpopulations could be isolated separately that were identified by immuno-chemistry and molecular hybridization assays as probable: (i) committed progenitors to hepatocytes; (ii) committed progenitors to bile ducts; or (iii) a mixed population of hemopoietic cells that contained a small percentage of hepatic blasts that are possibly pluripotent., The hepatic precursor cells have been characterized using immunochemistry, flow cytometry, and molecular hybridization assays.
The surgical modalities for the management of Budd-Chiari syndrome are associated with high morbidity and mortality. The clinical course of a patient with subacute Budd-Chiari syndrome and a myeloproliferative disorder is described in whom, to reduce the portal hypertension, a transjugular intrahepatic portosystemic stent-shunt (TIPS) was implanted. TIPS is a new, still experimental procedure for the treatment of patients with portal hypertension which is used mainly for patients with recurrent variceal bleeding. An intrahepatic metal wire stent connects a main branch of the portal vein with a large hepatic vein and reduces the portal venous pressure as a side-to-side portosystemic shunt. In the patient described here the implantation of a TIPS was followed by rapid reduction of ascites production and a continuing general improvement.
