Abstract
The transplantation of autologous BM-MSCs holds great potential for treating end-stage liver diseases. The aim of this study was to compare the efficiency of transplanted rBM-MSCs and rBM-MSC-derived differentiated stem cells (rBM-MSC-DSCs) for suppression of dimethylnitrosamine-injured liver damage in rat model. Synchrotron radiation Fourier-transform infrared (SR-FTIR) microspectroscopy was applied to investigate changes in the macromolecular composition. Transplantation of rBM-MSC-DSCs into liver-injured rats restored their serum albumin level and significantly suppressed transaminase activity as well as the morphological manifestations of liver disease. The regenerative effects of rBM-MSC-DSCs were corroborated unequivocally by the phenotypic difference analysis between liver tissues revealed by infrared spectroscopy. Spectroscopic changes in the spectral region from 1190–970 cm−1 (bands with absorbance maxima at 1150 cm−1, 1081 cm−1, and 1026 cm−1) indicated decreased levels of carbohydrates, in rBM-MSC-DSC-transplanted livers, compared with untreated and rBM-MSC--transplanted animals. Principal component analysis (PCA) of spectra acquired from liver tissue could readily discriminate rBM-MSC-DSC-transplanted animals from the untreated and rBM-MSC-transplanted animals. We conclude that the transplantation of rBM-MSC-DSCs effectively treats liver disease in rats and SR-FTIR microspectroscopy provides important insights into the fundamental biochemical alterations induced by the stem-derived cell transplantation, including an objective “signature” of the regenerative effects of stem cell therapy upon liver injury.
Highlights
Liver damage often leads to liver fibrosis which sometimes progresses to liver cirrhosis [1]
Wang et al used FTIR microspectroscopy to study the compositional changes in inflammatory cardiomyopathy, and the results demonstrate chemical difference between the inflammatory responses in the mouse model, providing insight into why the disease can be self-limiting in some cases while fatal in others [22]
Previous studies have reported that hepatocyte growth factor (HGF) upregulated C-X-C chemokine receptor type 4 (CXCR4), which is the chemokine receptor for stromal cellderived factor-1 (SDF-1), in human hematopoietic stem cells [35]
Summary
Liver damage often leads to liver fibrosis which sometimes progresses to liver cirrhosis [1]. Liver transplantation is one of the most effective treatments for severe liver-associated diseases such as cirrhosis. Due to the shortage of donated organs and the growing list of patients in need of such intervention, transplantation is often not a viable option [2]. Novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Most of the recent studies concentrate on stem cells of extrahepatic origin, as a potential derivation source for producing hepatocytes, because of their ready availability and unrestricted potential to propagate and differentiate [6,7,8,9]
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