HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/L1210    most recent 00427.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Denham, M. Articles by Mollard, R. Search for Related Content PubMed PubMed Citation Articles by Denham, M. Articles by Mollard, R.

Embryonic stem cells form glandular structures and express surfactant protein C following culture with dissociated fetal respiratory tissue

¹Monash Institute of Medical Research, Center for Early Human Development, Clayton, Melbourne; and ²Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

Submitted 6 October 2005 ; accepted in final form 4 January 2006

Mouse embryonic stem cells (MESCs) are pluripotent, theoretically immortal cells derived from the inner cell mass of developing blastocysts. The respiratory epithelium develops from the primitive foregut endoderm as a result of inductive morphogenetic interactions with the surrounding visceral mesoderm. After dissociation of the explanted fetal lung into single cells, these morphogenetic signaling pathways instruct reconstitution of the developing lung according to a process known as organotypic regeneration. Data presented here demonstrate that such fetal lung morphogenetic cues induce MESC derivatives to incorporate into the reforming pseudoglandular-like tubular ducts, display pan-keratin and surfactant protein C (Sftpc) immunoreactivity, and express Sftpc transcripts while displaying a normal diploid karyotype in coculture. The Sftpc inductive capacity of dissociated fetal lung tissue shows stage specificity with 24% of all MESC derivatives displaying Sftpc immunoreactivity after coculture with embryonic day 11.5 (E11.5) lung buds compared with 6% and 0.02% following coculture with E12.5 and E13.5 lung buds, respectively. MESC derivative Sftpc immunoreactivity follows a spatial and temporal specific maturation profile with an initially ubiquitous cellular Sftpc immunostaining pattern becoming apically polarized with time. Directing differentiation of MESCs into respiratory lineages has important implications for cell replacement therapeutics aimed at treating respiratory-specific diseases such as cystic fibrosis and idiopathic pulmonary fibrosis.

respiratory differentiation; coculture; morphogenetic cues

This article has been cited by other articles:

				T. van Haaften, R. Byrne, S. Bonnet, G. Y. Rochefort, J. Akabutu, M. Bouchentouf, G. J. Rey-Parra, J. Galipeau, A. Haromy, F. Eaton, et al. Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats Am. J. Respir. Crit. Care Med., December 1, 2009; 180(11): 1131 - 1142. [Abstract] [Full Text] [PDF]

				H. J. Rippon, S. Lane, M. Qin, N.-S. Ismail, M. R. Wilson, M. Takata, and A. E. Bishop Embryonic Stem Cells as a Source of Pulmonary Epithelium In Vitro and In Vivo Proceedings of the ATS, August 15, 2008; 5(6): 717 - 722. [Abstract] [Full Text] [PDF]

				D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop Stem Cells and Cell Therapies in Lung Biology and Lung Diseases Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667. [Full Text] [PDF]

				M. Denham, B. J. Conley, F. Olsson, L. Gulluyan, T. J. Cole, and R. Mollard A murine respiratory-inducing niche displays variable efficiency across human and mouse embryonic stem cell species Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1241 - L1247. [Abstract] [Full Text] [PDF]