Departments of Electron Microscopy, Theodor Bilharz Research Institute, Giza, Egypt.
APMIS. 2011 Jan;119(1):66-75. doi: 10.1111/j.1600-0463.2010.02693.x. Epub 2010 Nov 17.
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.
研究了移植的人脐血（UCB）CD133(+)干细胞在实验性慢性肝纤维化中的体内血管生成潜能，该肝纤维化是由小鼠血吸虫病引起的。富集的脐血来源的 CD133(+)细胞在原代培养基中培养 3 周。在感染小鼠血吸虫病 22 周后，达到慢性肝纤维化阶段后进行干细胞移植，3 周后处死小鼠。组织病理学和电子显微镜检查显示新形成的血管增加，而这种疾病阶段已知的纤维化减少。通过免疫组织化学分析，新形成的血管显示出人类特异性血管生成标志物 CD31、CD34 和血管性血友病因子的阳性表达。少数肝细胞样多角形细胞显示出人类血管内皮生长因子和诱导型一氧化氮合酶的阳性表达。移植的 CD133(+)人干细胞主要通过旁分泌方式增强肝血管生成和新血管生成，并通过创造有利于受损细胞增殖和存活的许可环境来促进修复，而不是直接分化为肝细胞。基于其造血和内皮分化能力，提示 CD133(+)细胞治疗在肝脏疾病中有双重优势。
