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.

Unlabelled: 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 after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI.

Serum lipid expression correlates with function and regeneration following living donor liver transplantation.

Following living donor liver transplantation (LDLT; and unlike deceased donor liver transplantation [DDLT]), the liver must rapidly regenerate, and sometimes segmental graft dysfunction (SGD) is observed. Hepatic regeneration requires substantial de novo lipid synthesis, and we previously reported that expression of lipid-related genes is dysregulated in LDLT. Here, we compare serum lipid measurements in 41 LDLT recipients and 43 DDLT recipients at baseline and at serial posttransplant time points.

Genomic profiles and predictors of early allograft dysfunction after human liver transplantation.

Early hepatic allograft dysfunction (EAD) manifests posttransplantation with high serum transaminases, persistent cholestasis, and coagulopathy. The biological mechanisms are poorly understood. This study investigates the molecular mechanisms involved in EAD and defines a gene expression signature revealing different biological pathways in subjects with EAD from those without EAD, a potential first step in developing a molecular classifier as a potential clinical diagnostic.

Support of hepatic regeneration by trophic factors from liver-derived mesenchymal stromal/stem cells.

Mesenchymal stromal/stem cells (MSCs) have multilineage differentiation potential and as such are known to promote regeneration in response to tissue injury. However, accumulating evidence indicates that the regenerative capacity of MSCs is not via transdifferentiation but mediated by their production of trophic and other factors that promote endogenous regeneration pathways of the tissue cells. In this chapter, we provide a detailed description on how to obtain trophic factors secreted by cultured MSCs and how they can be used in small animal models.

Heat shock protein 70 is required for optimal liver regeneration after partial hepatectomy in mice.

Liver regeneration is a complex process that restores functional tissue after resection or injury, and it is accompanied by transient adenosine triphosphate depletion and metabolic stress in hepatic parenchymal cells. Heat shock protein 70 (Hsp70) functions as a chaperone during periods of cellular stress and induces the expression of several inflammatory cytokines identified as key players during early liver regeneration. We, therefore, hypothesized that Hsp70 is required for the initiation of regeneration.