Research Article Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury Suomi M. G. Fouraschen, 1,2 Joshua H. Wolf, 2 Luc J. W. van der Laan, 1 Petra E. de Ruiter, 1 Wayne W. Hancock, 3 Job P. van Kooten, 1 Monique M. A. Verstegen, 1 Kim M. Olthoff, 2 and Jeroen de Jonge 1 1 Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands 2 Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USA 3 Department of Transplant Immunology, Pathology and Laboratory Medicine, Te Children’s Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA Correspondence should be addressed to Jeroen de Jonge; j.dejonge.1@erasmusmc.nl Received 9 April 2015; Accepted 27 May 2015 Academic Editor: Bjarne K. Møller Copyright © 2015 Suomi M. G. Fouraschen et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration afer partial hepatectomy. Tis study investigates if liver-derived MSC-secreted factors also promote liver regeneration afer resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrifced afer 6 or 24 hours (IRI group) or afer 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and infammatory cytokine gene expression showed no signifcant diferences between both treatment groups. In the IRI + PH model, signifcant reduction in hepatic tissue damage as well as a signifcant increase in hepatocyte proliferation was observed afer MSC-CM treatment. Conclusion. Mesenchymal stromal cell- derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure. 1. Introduction Advances in surgical techniques have enabled large liver resections as well as split and living donor liver transplanta- tion (LDLT). Transplantation of partial (living donor) liver grafs was introduced to help overcome donor organ scarcity and reduce waitlist mortality. Living donors undergo resec- tion of approximately 40–60% of their liver volume, which is transplanted into the recipient. Without the exceptional capacity of the liver to regenerate and thereby compensate for tissue loss and restore homeostasis, these extensive resections and partial graf transplantations would not be possible [1– 3]. Nevertheless, in case of adult to adult living donor liver transplantation both donors and partial graf recipients end up with a small-for-size liver, which is still associated with signifcant morbidity and even mortality [2, 4, 5]. In an attempt to decrease donor risk, smaller grafs (such as the lef lobe of the liver) can be used, but this is limited by the increased risk of the recipient to develop small-for-size syndrome [6]. In these settings, both loss of a substantial part of the liver mass and the inevitable ischemia and reperfusion injury (IRI) are major mechanisms of hepatic injury [7, 8]. Efective therapeutic strategies to protect against IRI, enhance regeneration, and stimulate recovery could minimize donor and recipient risk. Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 202975, 13 pages http://dx.doi.org/10.1155/2015/202975