PMID- 20950251 OWN - NLM STAT- MEDLINE DCOM- 20110721 LR - 20110228 IS - 1937-3392 (Electronic) IS - 1937-3384 (Linking) VI - 17 IP - 3 DP - 2011 Mar TI - Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice. PG - 359-66 LID - 10.1089/ten.TEC.2009.0519 [doi] AB - Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1 x 10(6) LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure. FAU - Forster, Natasha AU - Forster N AD - Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Fitzroy, Australia. FAU - Palmer, Jason A AU - Palmer JA FAU - Yeoh, George AU - Yeoh G FAU - Ong, Wei-Chen AU - Ong WC FAU - Mitchell, Geraldine M AU - Mitchell GM FAU - Slavin, John AU - Slavin J FAU - Tirnitz-Parker, Janina AU - Tirnitz-Parker J FAU - Morrison, Wayne A AU - Morrison WA LA - eng PT - Journal Article DEP - 20101130 PL - United States TA - Tissue Eng Part C Methods JT - Tissue engineering. Part C, Methods JID - 101466663 RN - 0 (Ki-67 Antigen) SB - IM MH - Animals MH - Blood Vessels/*metabolism MH - *Cell Differentiation MH - Cell Proliferation MH - Hepatocytes/*cytology MH - Ki-67 Antigen/metabolism MH - Liver/*cytology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Stem Cells/*cytology MH - Tissue Engineering/*instrumentation/*methods MH - Tissue Scaffolds EDAT- 2010/10/19 06:00 MHDA- 2011/07/22 06:00 CRDT- 2010/10/19 06:00 PHST- 2010/10/19 06:00 [entrez] PHST- 2010/10/19 06:00 [pubmed] PHST- 2011/07/22 06:00 [medline] AID - 10.1089/ten.TEC.2009.0519 [doi] PST - ppublish SO - Tissue Eng Part C Methods. 2011 Mar;17(3):359-66. doi: 10.1089/ten.TEC.2009.0519. Epub 2010 Nov 30.