CD133+ human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis

Elkhafif N, El Baz H, Hammam O, Hassan S, Salah F, Mansour W, Mansy S, Yehia H, Zaki A, Magdy R. CD133+ human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis. APMIS 2010. The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133+ stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133+ cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133+ human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133+ cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.