Graduate Student
Christian Metallo

• U. of Wisconsin-Madison Biotechnology Training Program Fellow

Thesis Research

Directed Differentiation of Human Embryonic Stem Cells to Epithelial Lineages

Engineered tissue constructs with regenerative capacity require large quantities of functional, lineage committed progenitors. Given their enhanced proliferative capacity and pluripotency, human embryonic stem cells (hESCs) are an attractive source of cells for tissue engineering. However, highly efficient processes must be developed to direct hESCs through developmental pathways to the appropriate lineages to exploit their technological potential. Formulation of such processes requires integration of engineering strategies with developmental biology concepts to effectively produce cells and tissues for scientific, diagnostic, and therapeutic use. Here we employ quantitative analysis of differentiated hESC populations to identify key signaling factors involved in ectodermal lineage specification; our primary focus is the generation of epithelial precursors that can be used to engineer regenerative constructs for the skin or related tissues. Application of retinoic acid (RA) to undifferentiated hESC populations, in conjunction with bone morphogenetic protein (BMP) signaling, efficiently mediates epithelial rather than neural differentiation. This differentiation process can be effectively used to generate essentially pure populations of hESC-derived keratinocytes under defined, feeder-free conditions. When coupled with the self-renewal capacity of hESCs, this method can produce large quantities of functional, non-transformed keratinocytes that retain the capacity to terminally differentiate and form coherent epithelial sheets.

Publications

1. Christian M. Metallo, Jeffrey C. Mohr, Christopher J. Detzel, Juan J. de Pablo, Bernard J. Van Wie, and Sean P. Palecek.
   "Engineering the Stem Cell Microenvironment".
   Biotechnology Progress 23(1):18-23, February 2007. [doi:10.1021/bp060350a] [ACS/BiotechnolProg]
2. Christian M. Metallo, Samira M. Azarin, Lin Ji, Juan J. de Pablo, and Sean P. Palecek.
   "Engineering Tissue from Human Embryonic Stem Cells".
   Journal of Cellular and Molecular Medicine, accepted, January 11, 2008. [doi:10.1111/j.1582-4934.2008.00228.x] [BlackwellSynergy/JCellMolMed]
3. Christian M. Metallo, Maxim A. Vodyanik, Juan J. de Pablo, Igor I. Slukvin, and Sean P. Palecek.
   "The response of human embryonic stem cell-derived endothelial cells to shear stress".
   Biotechnology and Bioengineering, in press, January 30, 2008. [doi:10.1002/bit.21809] [Wiley/BiotechBioeng]
4. Christian M. Metallo, Lin Ji, Juan J. de Pablo, and Sean P. Palecek.
   "Retinoic acid and bone morphogenetic protein signaling synergize to efficiently direct epithelial differentiation of human embryonic stem cells".
   Stem Cells 26(2):372-380, February 25, 2008. [doi:10.1634/stemcells.2007-0501] [AlphaMed/StemCells]

Other Publications

1. Liangzhi Xie, Warren Pilbrough, Christian M. Metallo, Tanya Zhong, Lana Pikus, John Leung, John G. Aunins, Weichang Zhou.
   "Serum-free suspension cultivation of PER.C6^® cells and recombinant adenovirus production under different pH conditions".
   Biotechnology and Bioengineering 80(5):569-79, December 5, 2002. [doi:10.1002/bit.10443]
2. Liangzhi Xie, Christian M. Metallo, James Warren, Warren Pilbrough, Joseph Peltier, Tanya Zhong, Lana Pikus, Amanda Yancy, John Leung, John G. Aunins, Weichang Zhou.
   "Large-scale propagation of a replication-defective adenovirus vector in stirred-tank bioreactor PER.C6 cell culture under sparging conditions".Biotechnology and Bioengineering 83(1):45-52, July 5, 2003. [doi:10.1002/bit.10644]

Contact

Mr. Christian M. Metallo
Department of Chemical and Biological Engineering
University of Wisconsin-Madison
3111 Engineering Hall
1415 Engineering Drive
Madison, WI 53706-1691
U.S.A.
tel: +1 608 265-4926
fax: +1 608 262-5434
email: cmetallo@wisc.edu