Abstract
We have recently shown that a multi-mineral extract from the marine red algae, Lithothamnion calcareum, suppresses colon polyp formation and inflammation in mice. In the present study, we used intact human colon tissue in organ culture to compare responses initiated by Ca2+ supplementation versus the multi-mineral extract. Normal human colon tissue was treated for 2 d in culture with various concentrations of calcium or the mineral-rich extract. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for levels of type I procollagen and type I collagen. At higher Ca2+ concentrations or with the mineral-rich extract, proliferation of epithelial cells at the base and walls of the mucosal crypts was suppressed, as visualized by reduced Ki67 staining. E-cadherin, a marker of differentiation, was more strongly expressed at the upper third of the crypt and at the luminal surface. Treatment with Ca2+ or with the multi-mineral extract influenced collagen turnover, with decreased procollagen and increased type I collagen. These data suggest that calcium or mineral-rich extract has the capacity to (1) promote differentiation in human colon tissue in organ culture and (2) modulate stromal function as assessed by increased levels of type I collagen. Taken together, these data suggest that human colon tissue in organ culture (supporting in vivo finding in mice) will provide a valuable model for the preclinical assessment of agents that regulate growth and differentiation in the colonic mucosa.
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Acknowledgments
This study was supported, in part, by grant 1R21CA140760 01 from the USPHAS. The authors would like to thank Deborah Postiff and Justin Reagan of the Tissue Procurement Core Laboratory, Comprehensive Cancer Center (Cancer Center Support Grant 5 P30 CA46592), as the source of the tissue specimens; Lisa Riggs (Histology Core) for her help with the preparation of tissue for histological examination; and Ron Craig (Histomorphometry Core) for his ScanScope service and assistance. Core laboratories are supported by the Department of Pathology at the University of Michigan.
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Dame, M.K., Veerapaneni, I., Bhagavathula, N. et al. Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation. In Vitro Cell.Dev.Biol.-Animal 47, 32–38 (2011). https://doi.org/10.1007/s11626-010-9358-3
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DOI: https://doi.org/10.1007/s11626-010-9358-3