7 To understand the mechanisms of liver diseases, development of three dimensional (3D) models will be useful in order to better recreate cell-cell interactions within their own microenvironment. 5, 6 This is clinically relevant and results in serious morbidity and mortality. ![]() 4 However, when the liver is severely damaged or hepatocyte proliferation is inhibited, the regenerative capacity is overwhelmed resulting in aberrant liver architecture and liver diseases. 1–3 The liver has an enormous capacity to regenerate through different cellular responses depending on the nature and severity of the injury. It is responsible for the production of acute phase proteins, complement components, cytokines and chemokines, and contains large, diverse populations of resident immune cells. The liver is an important organ required for metabolic activities, nutrient storage and detoxification. Keywords: scaffolds, tissue engineering, regenerative medicine, hepatocyte, chemokines, Matrigel, proteoglycan Abbreviations Based on our experience and results we do not believe that decellularized rat liver scaffolds are the ideal scaffolds for reproducible recellularization with human liver stem cells required for studying human liver regeneration or as in vitro models for pharmaceutical toxicity. ![]() A few cells expressed CYP3A7 but CYP3A4 was not found. Few cells expressed hepatocyte-specific markers cytokeratin (CK) 18 and CK8 but, with high variablilty, while but no expression of the biliary cell marker CK19 was found. The cells also showed expression of the endothelial marker L-SIGN and weak expression of human albumin. Approximately 50% of the human cells were viable at the end of recellularization with stable expression of human mitochondria. However, the cells were not evenly distributed in the scaffolds but found scattered as colonies in the rat parenchyma and blood vessels. Only in four of the recellularized rat scaffolds attachment of human HFLPC was seen. Even though the vascular network looked preserved after decellularization leakage was observed in majority of the livers. The portal veins were fragile at the end of the decellularization process, resulting in technical problems during recellularization. We found that, although the major extracellular proteins were preserved, cytokines/growth factors tested were significantly decreased in the decellularized livers. ![]() The ability of human liver sinusoidal endothelial cells (LSEC) and two previously well characterized human fetal liver progenitor cell (HFLPC) lines (SV40 and hFL4TERT) to repopulate the a cellular rodent liver tissues was evaluated. Here, we produced 3-D decellularized scaffolds from rat (n=32) livers preserving the native morphology and vascular structures with complete removal of cellular and nuclear materials. Identification of appropriate xenogeneic scaffolds which can support attachment, proliferation and differentiation of human cells is important for studying human organ regeneration. Decellularized organs with preserved architecture and vasculature have been created to produce customized bioengineered organs.
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