Enhanced liver progenitor cell survival and differentiation in vivo by spheroid implantation in a vascularized tissue engineering chamber

Abstract Liver tissue engineering is hampered by poor implanted cell survival due to inadequate vascularization and cell–cell/cell–matrix interactions. Here, we use liver progenitor cell (LPC) spheroids to enhance cell–cell/cell–matrix interactions, with implantation into an angiogenic in vivo mouse...

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Veröffentlicht in:Biomaterials 2013-05, Vol.34 (16), p.3992-4001
Hauptverfasser: Yap, Kiryu K, Dingle, Aaron M, Palmer, Jason A, Dhillon, Raminder S, Lokmic, Zerina, Penington, Anthony J, Yeoh, George C, Morrison, Wayne A, Mitchell, Geraldine M
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Sprache:eng
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Zusammenfassung:Abstract Liver tissue engineering is hampered by poor implanted cell survival due to inadequate vascularization and cell–cell/cell–matrix interactions. Here, we use liver progenitor cell (LPC) spheroids to enhance cell–cell/cell–matrix interactions, with implantation into an angiogenic in vivo mouse chamber. Spheroids were generated in vitro in methylcellulose medium. Day 2 spheroids were optimal for implantation (22,407 +/−645 cells/spheroid), demonstrating maximal proliferation (Ki67 immunolabeling) and minimal apoptosis (caspase-3 immunolabelling). In vivo chambers established bilaterally on epigastric vessels of immunodeficient mice were implanted with equivalent numbers of LPCs as a cell suspension (200,000 cells), or spheroids (9 spheroids). At day 14, a trend of increased LPC survival was observed in spheroid-implanted chambers [pan-cytokeratin (panCK+) cells, p  = 0.38, 2.4 fold increase)], with significantly increased differentiation [cytokeratin 18 (CK18+) cells, p  
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.02.011