Extrahepatic Stellate Cells

Previous studies using fluorescence microscopy, transmission electron microscopy, and electron microscopic autoradiography showed that cells that stored vitamin A distributed in extrahepatic organs, namely, lung, digestive tract, spleen, adrenal gland, testis, uterus, lymph node, thymus, bone marrow, adventitia of the aorta, lamina propria of the trachea, oral mucosa, and tonsil (Matano et al., 1999; Nagy et al., 1997; Wake, 1980). Morphology of these cells was similar to that of fibroblasts. These cells emanate autofluorescence of vitamin A and contain lipid droplets in the cytoplasm. These cells and HSCs form the SC system that regulates homeostasis of vitamin A in the whole body. Extrahepatic SCs also can synthesize and secrete ECM components.

Vitamin A distribution and content in tissues of a lamprey (Lampetra japonica) (Wold et al., 2004) (Fig. 14) and an arrowtooth halibut (Atheresthes evermanni) (Fig. 15) were analyzed. HSCs showed an abundance of vitamin A stored in lipid droplets in their cytoplasm. Similar cells storing vitamin A were present in the intestine, kidney, gill, and heart in both female and male lampreys. Morphological data obtained by gold chloride staining method, fluorescence microscopy, and transmission electron microscopy and HPLC quantification of vitamin A were consistent. The highest level of total vitamin A measured by HPLC was found in the intestine. The second and third highest concentrations of vitamin A were found in the liver and the kidney, respectively. These vitamin A-storing cells were not epithelial cells, but mesoderm-derived cells. Similar cells were distributed in the arrowtooth halibut. We propose as a hypothesis that these cells belong to the SC system (family) that stores vitamin A and regulates homeostasis of the vitamin in the whole body in these animals. Fibroblastic cells in the skin and somatic muscle stored little vitamin A. These results indicate that there is difference in the vitamin A-storing capacity between the splanchnic and intermediate mesoderm-derived cells (SCs) and somatic and dorsal mesoderm-derived cells (fibroblasts) in these animals. SCs derived from the splanchnic and intermediate mesoderm have high capacity and fibroblasts derived from the somatic and dorsal mesoderm have low capacity for the storage of vitamin A in these animals.

Pancreatic SCs, one sort of extrahepatic SCs, are now considered to be responsible for the induction of chronic pancreatitis and pancreatic fibrosis

FIGURE 14. Stellate cells in lamina propria of the intestine in lamprey (Lampetra japonica). Vitamin A-autofluorescence is detected in cells of the lamina propria (LP) (A). Gold chloride-reacted cells were distributed in the lamina propria (B and C). An electron micrograph showing membrane-bound (type I, A1) and nonmembrane-bound (type II, A2) lipid droplets (Wake, 1974) in a cell (SC) in the lamina propria of the intestine. E, epithelium; M, muscle; NF, unmyelinated nerve fiber; SM, submucosa; TA, typhlosolar artery. Scale bars indicate 5 mm (A-C) and 1 mm (D).

FIGURE 14. Stellate cells in lamina propria of the intestine in lamprey (Lampetra japonica). Vitamin A-autofluorescence is detected in cells of the lamina propria (LP) (A). Gold chloride-reacted cells were distributed in the lamina propria (B and C). An electron micrograph showing membrane-bound (type I, A1) and nonmembrane-bound (type II, A2) lipid droplets (Wake, 1974) in a cell (SC) in the lamina propria of the intestine. E, epithelium; M, muscle; NF, unmyelinated nerve fiber; SM, submucosa; TA, typhlosolar artery. Scale bars indicate 5 mm (A-C) and 1 mm (D).

(Apte et al., 1998; Bachem et al., 1998, 2002a,b; Masamune et al., 2002; Wells and Crawford, 1998). These extrahepatic SCs are now to be targets of the treatment of inflammation and organ fibrosis.

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