Fibroblasts alkaline phosphatase

Phosphorothioates generally protect normal tissues more than tumors. Tumor protection reported in some animal studies can pardy be explained by physiological effects of the particular dmgs, which are specific to rodents (4). WR-2721 does not appear to protect human and most animal tumors, apparentiy because of the low availabiUty of the dmg to tumor cells (4). Many tumors appear to have a reduced capillary density (44), which may mean that these tumors have altered levels of alkaline phosphatase, the enzyme that converts WR-2721 to WR-1065. A reduced abiUty of thiols to protect the hypoxic cells characteristic of many tumors may also contribute to their selectivity for normal tissues. The observation that WR-1065 protects cultured normal human fibroblasts, but not fibrosarcoma tumor cells, suggests that additional factors may contribute to the selectivity of radioprotection by WR-2721 m vivo (18). 

Regulation of alkaline phosphatase activity was discussed by Cox and Griffin 65). Steroids such as hydrocortisone or prednisolone (1 (ig/ml of medium) can induce a 3- to 20-fold rise in certain HeLa cell cultures, while other cell lines are induced by 15 mM phenyl phosphate. Recently, it has been shown that fibroblast cell cultures are also stimulated by prednisolone (( ( ). According to one report, Pi may have a control function here a decrease in the level of rat kidney P produced by a low phosphate diet was accompanied by an increase in alkaline phosphatase. Nine other enzymes monitored were unaffected 67). 

Fedde, K.N. and Whyte, M.P. (1990) Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5 -phosphate ectophosphate normal and hypo-phosphatasia fibroblast study. American Journal ofEiuman Genetics 47, 757-775. 

Bellows, C. G., Anbin, J. E., and Heersche, J. N. 1991. Initiation and progression of mineralization of bone nodules formed in vitro The role of alkaline phosphatase and organic phosphate. Bone Miner. 14 27-40. Berscht, P. C., Nies, B., Liebendorfer, A., and Kreuter, J. 1994. Incorporation of basic fibroblasts growth factor into methylpyrroidone chitosan fleeces and determination of the in vitro release characteristics. Biomaterials 15 593-600. 

Almeida, M.J., Pereira, L., Milet, C., Haigle, J., Barbosa, M., Lopez, E., 2001. Comparative effects of nacre water-soluble matrix and dexamethasone on the alkaline phosphatase activity of MRC-5 fibroblasts. J. Biomed. Mater. Res. 57, 306-312. 

An enzyme which splits a-glycerophosphate at a pH of about 5.0 has also been studied, although not as extensively as alkaline phosphatase. It has been found that this enzyme is present in cytoplasmic granules in fibroblasts of a variety of mammals. The enzyme is widely distributed in the nervous system. Shimizu found the reaction most intense in the axone... 

PCL has been investigated as a stabilizing polymer on PGA scaffolds to aid in the formation of spherical aggregates by human biliary epithelial cells (hBEC). These hBECs proliferated on the synthetic scaffold and expressed phenotypic proteins, indicating cell stability [63]. Further studies of PCL as a homopolymer has been demonstrated to support human osteoblast and dermal fibroblast cell viabihty [65,66]. The results with osteoblasts on porous PCL has shown a production of alkaline phosphatase, a marker of bone mineralization [65], Also, dermal fibroblasts on mechanically stretched PCL films proliferated and maintained their rounded morphology [66]. 

---