| Organ-specific scaffolds for in vitro expansion, differentiation and organization of primary lung cells. | |
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MedLine Citation:
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PMID: 21457099 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In light of the increasing need for differentiated primary cells for cell therapy and the rapid de-differentiation occurring during standard in vitro cultivation techniques, there is an urgent need for developing 3-dimensional in vitro systems where expanded cells display in vivo-like differentiated phenotypes. It is becoming clear that the natural microenvironment provides the optimal conditions for achieving this aim. To this end, we prepared natural decellularized scaffolds of microscopic dimensions that would allow appropriate diffusion of gases and nutrients to all seeded cells. Scaffolds from either the lung or the liver were analyzed for their ability to support growth and differentiation of progenitor alveolar cells and hepatocytes. We observed that progenitor alveolar cells that have been expanded on plastic culture and thus de-differentiated, grew within the lung-derived scaffolds into highly organized structures, and regained differentiation markers classical for type I- and type II alveolar cells. The cells generated proper alveolar structures, where only 15-30% of them secreted surfactant proteins in a localized manner for extended periods. Vice versa, liver-derived scaffolds supported the differentiation state of primary hepatocytes. We further demonstrate that the natural scaffolds are organ specific, where only cells derived from the same organ become properly differentiated. A proteomic analysis shows significant different composition of lung and liver scaffolds, where decorin, thrombospondin 1, vimentin and various laminin isoforms are especially enriched in the lung. Altogether, our data demonstrate that complex interactions between the seeded cells and a highly organized, organ-specific stroma are required for proper localized cell differentiation. Thus, our novel in vitro culture system can be used for ex vivo differentiation and organization of expanded primary cells. |
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Authors:
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Yulia Shamis; Eilat Hasson; Avigail Soroker; Elad Bassat; Yael Shimoni; Tamar Ziv; Ronit Vogt Sionov; Eduardo Mitrani |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-2 |
Journal Detail:
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Title: Tissue engineering. Part C, Methods Volume: - ISSN: 1937-3392 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101466663 Medline TA: Tissue Eng Part C Methods Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Hebrew University of Jerusalem, Department of Cellular and Developmental Biology, Jerusalem, Israel; yulia.shamis@tufts.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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