Ultrastructural Study of Hepatic Changes after Human Umbilical Cord Blood Stem Cell Transplantation in Chronic Murine Schistosomiasis
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- Category: Vol. 79, September 2011
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Ultrastructural Study of Hepatic Changes after Human Umbilical Cord Blood Stem Cell Transplantation in Chronic Murine Schistosomiasis,HALA N. HOSNI, HODA A. YEHIA and RANYA M. EL-SHEIKH
Abstract
Background: The contribution of hematopoietic stem cells to liver therapy in different forms of liver injury remains debatable. In the last decade, the number of transplantations of hematopoietic cells derived from cord blood has increased, where numerous literature reports documented the feasibility and effectiveness of the transplantation of cord blood for the treatment of a broad range of disorders.
Aim of the Work: This xenogenic research is designed to highlight, by light and electron microscopic study, the possi-bility of engraftment of human umbilical cord blood derived stem cells in the livers of immune-competent mice infected with chronic schistosomiasis.
Material and Methods: This study was conducted on 20 Swiss Albino immune-competent mice. The mice were subdi-vided into four groups (5 mice each). (Group 1) was infected with Schistosoma mansoni cercariae for 20 weeks’ duration, then intrahepatically transplanted with CD133+ human cord blood mononuclear cells, cultured on nutrient media, and isolated using the MACS Separation Unit from Miltenyi Biotec. (Group 2) was infected with S.mansoni, but not transplanted, (group 3) was normal and transplanted, and (group 4) was normal and non transplanted. All mice were sacrificed 3 weeks following the transplantation of groups 1 and 3. Engraftment of transplanted human cells was assessed by means of immunohistochemistry; using antibodies against human Hep Par 1 and a-fetoprotein. Histological examination was performed using the Zeiss light microscope, and ultra-structural study was carried out by the Philips TEM 208 S electron microscope.
Results: By light microscopic examination, livers of the infected transplanted group (group 1) and the infected non transplanted group (group 2) showed variable sized fibrocel-lular and fibrous schistosomal granulomas. (Group 1) exhibited as well more prominent bile duct proliferation than (group 2). Sections of (groups 1 & 3) showed small and large eosi-nophilic cells different from the surrounding murine hepato-cytes. By immunohistochemistry, some cells in (group 1 & 3) sections showed positive cytoplasmic staining for the two anti human hepatocyte markers used; (Hep Par 1 and afetoprotein). Electron microscopic examination of (group 1) grids distinguished variable immature cells in the form of small progenitor cells, intermediate hepatocyte-like oval cells and larger premature hepatocytic cells. The transplanted healthy group (group 3) showed similar cells. The previously noted cells were not seen in the remaining control groups, (groups 2 & 4).
Conclusion: This research proved engraftment of the human umbilical cord blood hematopoietic stem cells after their intrahepatic transplantation into the livers of mice suffering from chronic hepatic schistosomiasis, and their attempt to give rise to premature forms of cells with hepatocytic lineage. Extensive studies are still needed to clarify the possible utility of these cells in resolving damaged organs and tissues.