Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 101, Issue 4, Pages 932-941Publisher
WILEY-BLACKWELL
DOI: 10.1002/jbm.a.34391
Keywords
scaffold; bioluminescence imaging; cell differentiation; angiogenesis; mesenchymal stromal cells
Funding
- European Community [NMP-LA-2008-214402]
- Spanish Government [SAF2009-07102]
- University and Research Commission for Innovation
- University and Company Department (Government of Catalonia)
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The angiogenic capacity of a new biomaterial composite of poly(lactic acid) and calcium phosphate glass (PLA/CaP) was analyzed by noninvasive bioluminescence imaging (BLI) and histological procedures. Human adipose tissue-derived mesenchymal stromal cells expressing cytomegalovirus (CMV) promoter regulated Photinus pyralis luciferase (hAMSC-PLuc) grew up to 30 times the initial cell load, in vitro, when seeded in PLA/CaP scaffolds, but suffered an initial growth crisis followed by recovery when the scaffolds were subcutaneously implanted in SCID mice. To analyze changes in gene expression, hAMSC-PLuc cells were double labeled with a CMV promoter regulated Renilla reniformis luciferase and a Photinus pyralis luciferase reporter regulated by either the PECAM promoter or a hypoxia response element (HRE) artificial promoter and seeded in PLA/CaP and PLA scaffolds implanted in SCID mice. Analysis by BLI showed that hAMSCs in scaffolds were induced to differentiate to the endothelial lineage and did this faster in PLA/CaP than in PLA scaffolds. Endothelial differentiation correlated with a decrease in the activity of HRE regulated luciferase expression, indicative of a reduction of hypoxia. Histological analysis showed that PLA/CaP scaffolds were colonized by a functional host vascular system. Moreover, colonization by isolectin B4 positive host cells was more effective in PLA/CaP than in PLA scaffolds, corroborating BLI results. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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