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3. Hedgehog signaling maintains resident hepatic progenitors throughout life

Author

Sicklick, Jason K., Li, Yin-Xiong, Melhem, Alaa, Schmelzer, Eva, Zdanowicz, Marzena, Huang, Jiawen, Caballero, Montserrat, Fair, Jeff H., Ludlow, John W., McClelland, Randall E., Reid, Lola M., and Diehl, Anna Mae

Subjects
Genetic transcription -- Research, Hedgehogs -- Health aspects, Hedgehogs -- Genetic aspects, Biological sciences
Abstract

Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stein cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage. Indian hedgehog; liver; Patched; progenitor cell; Sonic hedgehog

Published
2006

4. Tissue Engineering

Author

McClelland, Randall E., primary, Dennis, Robert, additional, Reid, Lola M., additional, Stegemann, Jan P., additional, Palsson, Bernard, additional, and Macdonald, Jeffrey M., additional

Published
2012
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6. List of Contributors

Author

Ahlstrom, Jon D., primary, Ahsan, Taby, additional, Allickson, Julie, additional, Almarza, Alejandro J., additional, Anderson, James M., additional, Andrews, Peter, additional, Aslan, Hadi, additional, Atala, Anthony, additional, Badylak, Stephen F., additional, Batra, Ashok, additional, Baumann, M. Douglas, additional, Bellamkonda, Ravi V., additional, Bergman, Nicole M., additional, Beyhan, Z., additional, Bhatia, Mickie, additional, Bhatia, Sangeeta N., additional, Black, Peter M., additional, Blau, Helen, additional, Boden, Scott D., additional, Brey, Eric M., additional, Brivanlou, Ali H., additional, Brown, Chris R., additional, Bruder, Scott P., additional, Chambers, S.M., additional, Chen, Christopher S., additional, Chen, LiHow, additional, Chen, Mike, additional, Chen, Sulin, additional, Cheng, N., additional, Christ, George J., additional, Chung, Seyung, additional, Cibelli, J.B., additional, Cimini, Massimo, additional, De Coppi, Paolo, additional, Dodla, Mahesh C., additional, Dominguez-Bendala, Juan, additional, Doyle, AM, additional, Durfor, Charles N., additional, Echelard, Yann, additional, Effros, Rita B., additional, Elisseeff, Jennifer, additional, Ellis, Ewa C.S., additional, Emamaullee, Juliet A., additional, Erickson, Carol A., additional, De Filippo, Roger, additional, Fink, Donald, additional, Fissell, William H., additional, Friedlaender, Gary E., additional, Furth, Mark E., additional, Gafni, Yossi, additional, Gage, Keneth, additional, Garcia, Andres, additional, Gavin, William, additional, Gazit, Daniel, additional, Gazit, Zulma, additional, Gemmiti, Christopher S., additional, Gerlach, Jörg C., additional, Gokhale, Paul J., additional, Goodell, M.A., additional, Griffith, May, additional, Guenin, Louis M., additional, Giuliani, Stefano, additional, Guldberg, Robert E., additional, Hacker, M.C., additional, Harrison, Benjamin S., additional, Hartmann, Bernd, additional, Hilbert, Stephen H., additional, Hillel, Alexander, additional, Hipp, Jason, additional, Holcomb, Col. J.B., additional, Hollinger, Jeffrey O., additional, Holy, Chantal E., additional, Hout, Mariah, additional, Hu, Jiang, additional, Huang, George T.-J., additional, Huard, Johnny, additional, Hui, Elliot E., additional, Humes, H. David, additional, Intaglietta, Marcos, additional, Ji, Junfeng, additional, Jiang, Yueha, additional, Johnen, Christa, additional, Johnston, Josephine, additional, Joraku, Akira, additional, Kaplan, David L., additional, Kaplan, David S., additional, Khang, Gilson, additional, Khanzada, Rehan N., additional, Kim, Soon Hee, additional, Kim, Moon Suk, additional, Kimelman, Nadav, additional, Klimanskaya, Irina, additional, Kluge, Jonathan A., additional, Kolambkar, Yash, additional, Koh, Chester J., additional, Komura, Makoto, additional, Kondziolka, Douglas, additional, Konya, Deniz, additional, Kues, Wilfried A., additional, Kwong, Francois Ng kee, additional, Lamba, Deepak, additional, Lee, Hai Bang, additional, Lee, Hyukjin, additional, Leisk, Gary G., additional, Leong, Kam W., additional, Levine, Ariel J., additional, Li, Ren Ke, additional, Li, Wan-Ju, additional, Lim, Grace J., additional, Lin, Yan, additional, Lindblad, William J., additional, Liu, Wendy F., additional, Liu, Xiaohua, additional, Lucas-Hahn, Andrea, additional, Luttun, Aernout, additional, Lynch, Samuel, additional, Ma, Peter X., additional, Maher, Ellen, additional, Martins-Green, Manuela, additional, McClelland, Randall E., additional, McFarland, Richard, additional, McIntire, Larry V., additional, Meade, Harry, additional, Melican, David L., additional, Mikos, A.G., additional, Montoya, Fernando Ulloa, additional, Nerem, Robert M., additional, Niemann, Heiner, additional, Nori, Aparna, additional, Pabst, Patrea L., additional, Park, Kook In, additional, Park, Tae Gwan, additional, Patterson, David P., additional, Pauwelyn, Karen, additional, Pelled, Gadi, additional, Perin, Laura, additional, Petreaca, M., additional, Pileggi, Antonello, additional, Pomerantz, Jason H., additional, Porter, Blaise, additional, Radisic, Milica, additional, Ratner, Buddy D., additional, Reddi, A. Hari, additional, Reh, Thomas A., additional, Reid, Lola M., additional, Ricordi, Camillo, additional, Ross, Jeff, additional, Russell, Alan J., additional, Santos, Filipe N.C., additional, Schmitz, John P., additional, Schuch, Gunter, additional, Sedrakyan, Sargis, additional, Sefton, Michael V., additional, Serafini, Marta, additional, Shah, Paulesh, additional, Shapiro, A.M. James, additional, Sheardown, Heather, additional, Shoichet, Molly S., additional, Siddiqui, M. Minhaj, additional, Sidman, Richard L., additional, Silverman, Ronald, additional, Skuk, Daniel, additional, Snyder, Evan, additional, Soker, Shay, additional, Spector, Myron, additional, Stocum, David L., additional, Strom, Stephen C., additional, Taylor, Doris A., additional, Teng, Yang D., additional, Thomson, James, additional, Tranquillo, Robert T., additional, Tremblay, Jacques P., additional, Tsai, Amy, additional, Tuan, Rocky S., additional, Tubo, Ross S., additional, Van Dyke, Mark, additional, Vavoie, Deborah, additional, Verfaillie, Catherine, additional, Volenec, F. Jerry, additional, Wargo, Sara, additional, Warnwath, Joseph W., additional, Wechsler, Lawrence, additional, Wei, Shen, additional, Weisel, Richard D., additional, West, Jennifer L., additional, Williams, Chrysanthi, additional, Williams, J. Koudy, additional, Witten, Celia, additional, Wolf, Steven E., additional, Woo, Savio L.-Y., additional, Wosnick, Jordan H., additional, Wrenzycki, Christine, additional, Xaymardan, Munira, additional, Yao, Hsin-Lei, additional, Yazdani, Saami K., additional, Yelick, Pamela C., additional, Yoo, James J., additional, Yu, Junying, additional, Zeilinger, Katrin, additional, Zeng, Lepeng, additional, Zenovich, Andrey G., additional, Zhong, Bonan, additional, Ziomek, Carol A., additional, and Zoloth, Laurie, additional

Published
2008
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7. Use of Micropathways to Improve Oxygen Transport in a Hepatic System

Author

McClelland, Randall E. and Coger, Robin N.

Subjects
Biomechanics -- Research, Artificial liver -- Research, Engineering and manufacturing industries, Science and technology
Abstract

Establishing suitable oxygen transport pathways within bioartificial liver replacement devices continues to be an important engineering challenge. Oxygen delivery is critical since this is one of the nutrients necessary to maintain hepatocyte viability and function. In the current study, the microporosity of a collagen extracellular matrix has been modified to permit both diffusion and convection mass transport. Using fluorescent visualization, the enhancement technique was found to extend the oxygen transport distance from 170 [micro]m to 360 [micro]m. Furthermore, in hepatocyte culture studies, the enhancement technique was observed to yield a sixfold increase in the amount of viable hepatocytes able to be sustained by a single [O.sub.2] source. Normalized function studies confirm that hepatocyte function was also improved in the enhanced collagen configurations. [S0148-0731(00)00903-1]

Published
2000

8. Hepatic stem cells and hepatoblasts : identification, isolation, and ex vivo maintenance

Author

Wauthier, Eliane, Schmelzer, Eva, Turner, William, Zhang, Lili, LeCluyse, E, Ruiz, Joseph, Turner, Rachael, Furth, Mark E., Kubota, Hiroshi, Lozoya, Oswaldo, Barbier, Claire, McClelland, Randall E, Yao, Hsin Lei, Moss, Nicholas, Bruce, Andrew, Ludlow, John, Reid, Lola M., Wauthier, Eliane, Schmelzer, Eva, Turner, William, Zhang, Lili, LeCluyse, E, Ruiz, Joseph, Turner, Rachael, Furth, Mark E., Kubota, Hiroshi, Lozoya, Oswaldo, Barbier, Claire, McClelland, Randall E, Yao, Hsin Lei, Moss, Nicholas, Bruce, Andrew, Ludlow, John, and Reid, Lola M.

Published
2008

9. In-Vivo Imaging Of Transplanted Human Hepatic Stem Cells: Negative Contrast Labeling And 7t Micro-MRI Tracking

Author

NORTH CAROLINA UNIV AT CHAPEL HILL SCHOOL OF MEDICINE, McClelland, Randall E., Wauthier, Eliane, Reid, Lola, Hsu, Edward, NORTH CAROLINA UNIV AT CHAPEL HILL SCHOOL OF MEDICINE, McClelland, Randall E., Wauthier, Eliane, Reid, Lola, and Hsu, Edward

Abstract

Stem cell therapies have great potential as alternative options to whole organ transplantations in treating dysfunction or failure, and alleviating the chronic shortage of donor availability of organs such as the liver. In these therapies, adherent stem cells are transplanted to replace and repopulate diseased tissues, hence allowing the failing organs to regain their functional effectiveness. Given that clinical trials are ongoing or are about to occur with many different categories of stem cells, there is a need for in vivo stem cell imaging to monitor cell motility after inoculation, and to follow the location and expansion of the stem cells thereafter. Specifically, some topics being addressed comprise cell transplantation procedures, cell migration dynamics, and possibilities for creating tissue-cell-vacuums to permit engraftment and expansion of the transplanted cells. In this way, the efficacy of stem cell therapy may be evaluated and realized. The goals of the current study are to develop effective procedures for labeling stem cells with contrast agents for magnetic resonance imaging (MRI), and to investigate the MRI detectability of labeled cells. The model systems are human hepatic stem cells that are isolated by fractionation or immunoselection technologies from human fetal livers. In brief, there are two subpopulations of human hepatic stem cells, both of which are positive for Epithelial Cell Adhesion molecule (EpCAM) as well as for other antigens (Moss, Wauthier et al. 2004). The uptake, retention and physiological effects of magnetic labels are examined with in vitro experiments. Subsequently, the human hepatic stem cells are transplanted into immunocompromised SCID/nod mice to monitor in vivo MRI cell signals. To facilitate time-lapse investigations, several animals are inoculated simultaneously but independently imaged in order to quantify signal intensities, durations, and spatial distributions of cells within resident mice livers., See also ADM001736. Proceedings for the Army Science Conference (24th) Held on 29 November - 2 December 2004 in Orlando, Florida. The original document contains color images. Prepared in collaboration with Duke University, Durham, NC.

Published
2004

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