Injury-dependent retention of intraportally administered mesenchymal stromal cells following partial hepatectomy of steatotic liver does not lead to improved liver recovery.

Abstract

The aim of this study was to evaluate the effect of bone marrow-derived mesenchymal stromal cell (BM-MSC) administration on liver function following partial hepatectomy (PHx) of methionine/choline-deficient (MCD) diet induced steatotic livers in rodents. Here we identified and validated serum cholinesterase (CHE) and triglyceride (TG) levels as non-invasive markers to longitudinally monitor rat liver function. Using in vivo bioluminescence imaging, retention of BM-MSC in the liver was observed following intraportal administration, but not after intravenous administration. Therefore, BM-MSC were intraportally delivered to investigate the effect on liver recovery and/or regeneration after PHx. However, despite recovery to normal body weight, liver weight and NAS score, both serum CHE and TG levels of non-treated and cell-treated rats with PHx after MCD diet remained significantly lower as compared to those of control rats. Importantly, serum CHE levels, but not TG levels, of cell-treated rats remained significantly lower as compared to those of non-treated rats, thereby warranting that certain caution should be considered for future clinical application of IP BM-MSC administration in order to promote liver regeneration and/or function.