Document Detail

Spatial and temporal analysis of extracellular matrix proteins in the developing murine heart: a blueprint for regeneration.
MedLine Citation:
PMID:  23273220     Owner:  NLM     Status:  MEDLINE    
The extracellular matrix (ECM) of the embryonic heart guides assembly and maturation of cardiac cell types and, thus, may serve as a useful template, or blueprint, for fabrication of scaffolds for cardiac tissue engineering. Surprisingly, characterization of the ECM with cardiac development is scattered and fails to comprehensively reflect the spatiotemporal dynamics making it difficult to apply to tissue engineering efforts. The objective of this work was to define a blueprint of the spatiotemporal organization, localization, and relative amount of the four essential ECM proteins, collagen types I and IV (COLI, COLIV), elastin (ELN), and fibronectin (FN) in the left ventricle of the murine heart at embryonic stages E12.5, E14.5, and E16.5 and 2 days postnatal (P2). Second harmonic generation (SHG) imaging identified fibrillar collagens at E14.5, with an increasing density over time. Subsequently, immunohistochemistry (IHC) was used to compare the spatial distribution, organization, and relative amounts of each ECM protein. COLIV was found throughout the developing heart, progressing in amount and organization from E12.5 to P2. The amount of COLI was greatest at E12.5 particularly within the epicardium. For all stages, FN was present in the epicardium, with highest levels at E12.5 and present in the myocardium and the endocardium at relatively constant levels at all time points. ELN remained relatively constant in appearance and amount throughout the developmental stages except for a transient increase at E16.5. Expression of ECM mRNA was determined using quantitative polymerase chain reaction and allowed for comparison of amounts of ECM molecules at each time point. Generally, COLI and COLIII mRNA expression levels were comparatively high, while COLIV, laminin, and FN were expressed at intermediate levels throughout the time period studied. Interestingly, levels of ELN mRNA were relatively low at early time points (E12.5), but increased significantly by P2. Thus, we identified changes in the spatial and temporal localization of the primary ECM of the developing ventricle. This characterization can serve as a blueprint for fabrication techniques, which we illustrate by using multiphoton excitation photochemistry to create a synthetic scaffold based on COLIV organization at P2. Similarly, fabricated scaffolds generated using ECM components, could be utilized for ventricular repair.
Kevin P Hanson; Jangwook P Jung; Quyen A Tran; Shao-Pu P Hsu; Rioko Iida; Visar Ajeti; Paul J Campagnola; Kevin W Eliceiri; Jayne M Squirrell; Gary E Lyons; Brenda M Ogle
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-14
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  19     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-03-27     Completed Date:  2013-09-30     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1132-43     Citation Subset:  IM    
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MeSH Terms
Collagen Type I / genetics,  metabolism
Collagen Type III / metabolism
Elastin / genetics,  metabolism
Extracellular Matrix Proteins / genetics,  metabolism*
Fibronectins / genetics,  metabolism
Heart / embryology*
Heart Ventricles / embryology,  metabolism
Pericardium / embryology,  metabolism
Real-Time Polymerase Chain Reaction
Regeneration / physiology
Grant Support
Reg. No./Substance:
0/Collagen Type I; 0/Collagen Type III; 0/Extracellular Matrix Proteins; 0/Fibronectins; 9007-58-3/Elastin

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