[Show abstract][Hide abstract] ABSTRACT: Tissue-derived stem cells may offer future liver disease therapies. The developing human liver provides an excellent model to examine normal hepatic progenitor cell maturation, but candidate populations are poorly characterized. We sought to identify putative progenitor phenotypes in first-trimester human liver, by characterizing the architectural relationship between developing epithelial, mesenchymal, and hematopoietic lineages. Bipotential hepatoblasts were identified by co-expression of hepatocytic (cytokeratin 18, albumin) and biliary(cytokeratin 19) specific markers and epithelial-specific E-cadherin. Restriction of dlk/pref-1 expression to hepatoblasts identifies this as a novel human marker allowing for hepatoblast sorting for in vitro analysis. Furthermore, the liver stem cell and haematopoietic marker Thy-1 was co-expressed with markers of hematopoietic (CD34) and mesenchymal (vimentin) lineage restriction on portal vein endothelium. Therefore, this structure may constitute a novel progenitor compartment with hemangioblast-like properties.
Stem Cells and Development 11/2007; 16(5):771-8. DOI:10.1089/scd.2007.0016 · 3.73 Impact Factor
Biomimetics: Advancing Nanobiomaterials and Tissue Engineering Bonded Systems., Edited by Ramalingam M, Wang X, Chen G, Ma P, Cui F, 01/2013: chapter Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering.: pages 119-62.; Wiley-Scrivener.
[Show abstract][Hide abstract] ABSTRACT: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing.
A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography.
AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84.
Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.
Nima Aghaeepour, Pratip Chattopadhyay, Maria Chikina, Tom Dhaene, Sofie Van Gassen, Miron Kursa, Bart N Lambrecht, Mehrnoush Malek, Yu Qian, Peng Qiu, [...], Dong Tong, Celine Vens, Sławomir Walkowiak, Kui Wang, Greg Finak, Raphael Gottardo, Tim Mosmann, Garry P Nolan, Richard H Scheuermann, Ryan R Brinkman
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