Abstract
BackgroundMesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis. However, efficient cell delivery method is urgently needed and the therapeutic mechanism remains unclear. This study focused on developing a minimally invasive open-flow microperfusion (OFM) technique, which combined orthotopic transplantation of human umbilical cord-derived (hUC)-MSCs to liver and in vivo monitoring of liver microenvironment in mice with CCl4-induced liver fibrosis.MethodsThe therapeutic potential of OFM route was evaluated by comparing OFM with intravenous (IV) injection route in terms of hUC-MSCs engraftment at the fibrosis liver, liver histopathological features, liver function and fibrotic markers expression after hUC-MSCs administration. OFM was also applied to sample liver interstitial fluid in vivo, and subsequent metabolomic analysis was performed to investigate metabolic changes in liver microenvironment.ResultsCompared with IV route, OFM route caused more hUC-MSCs accumulation in the liver and was more effective in improving the remodeling of liver structure and reducing collagen deposition in fibrotic liver. OFM transplantation of hUC-MSCs reduced blood ALT, AST, ALP and TBIL levels and increased ALB levels, to a greater extent than IV route. And OFM route appeared to have a more pronounced effect on ameliorating the CCl4-induced up-regulation of the fibrotic markers, such as α-SMA, collagen I and TGF-β. In vivo monitoring of liver microenvironment demonstrated the metabolic perturbations induced by pathological condition and treatment intervention. Two metabolites and eight metabolic pathways, which were most likely to be associated with the liver fibrosis progression, were regulated by hUC-MSCs administration.ConclusionThe results demonstrated that the novel OFM technique would be useful for hUC-MSCs transplantation in liver fibrosis treatment and for monitoring of the liver metabolic microenvironment to explore the underlying therapeutic mechanisms.
Highlights
Mesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis
open-flow microperfusion (OFM) route allowed a greater number of transplanted cells to seed into the fibrotic liver OFM is a minimally invasive, universal and continuous in vivo sampling technique, which is widely used in sampling interstitial fluid components via macroscopic holes without nominal cut-off value [25]
Metabolomic analysis of liver dialysates obtained by OFM sampling was performed to investigate metabolic changes in liver microenvironment.Our results showed that compared with IV, OFM route caused more human umbilical cord-derived (hUC)-MSCs accumulation in the liver
Summary
Mesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis. Efficient cell delivery method is urgently needed and the therapeutic mechanism remains unclear. This study focused on developing a minimally invasive open-flow microperfusion (OFM) technique, which combined orthotopic transplantation of human umbilical cord-derived (hUC)-MSCs to liver and in vivo monitoring of liver microenvironment in mice with C Cl4-induced liver fibrosis. The chronic injuries lead to a wound-healing response, which is characterized by a switch of hepatic stellate cells (HSCs) from quiescent to an activated myofibroblastlike phenotype [3]. Liver transplantation seems to be a preferred strategy, there remain a number of challenges in this method, including shortage of donor organs, immune rejection response and surgery complications [8, 9]. It is urgent to search for an alternative treatment strategy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
