Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury.

BACKGROUND: Stem cell transplantation provides a theoretical approach for liver regeneration medicine; it may promote liver regeneration and self-repair. However, the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated. This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl4 injury. METHODS: Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation, characterized by cytoflow immunofluorescence, and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl4. The integration of bone marrow cells into the liver was examined microscopically, and plasma hepatic enzymes were determined biochemically. RESULTS: Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells. Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl4-treated mice. Densitometry showed increased in situ cell proliferation (50+/-14 vs 20+/-3 cells/high-power field, P<0.05) and albumin expression (149+/-25 vs 20+/-5 cells/high-power field, P<0.05) in the liver, as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls. CONCLUSIONS: Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver. Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.

Development of a Prognostic Signature Based on Single-Cell RNA Sequencing Data of Immune Cells in Intrahepatic Cholangiocarcinoma.

Analysis of single-cell RNA sequencing (scRNA-seq) data of immune cells from the tumor microenvironment (TME) may identify tumor progression biomarkers. This study was designed to investigate the prognostic value of differentially expressed genes (DEGs) in intrahepatic cholangiocarcinoma (ICC) using scRNA-seq. We downloaded the scRNA-seq data of 33,991 cell samples, including 17,090 ICC cell samples and 16,901 ICC adjacent tissue cell samples regarded as normal cells. scRNA-seq data were processed and classified into 20 clusters. The immune cell clusters were extracted and processed again in the same way, and each type of immune cells was divided into several subclusters. In total, 337 marker genes of macrophages and 427 marker genes of B cells were identified by comparing ICC subclusters with normal subclusters. Finally, 659 DEGs were obtained by merging B cell and macrophage marker genes. ICC sample clinical information and gene expression data were downloaded. A nine-prognosis-related-gene (PRG) signature was established by analyzing the correlation between DEGs and overall survival in ICC. The robustness and validity of the signature were verified. Functional enrichment analysis revealed that the nine PRGs were mainly involved in tumor immune mechanisms. In conclusion, we established a PRG signature based on scRNA-seq data from immune cells of patients with ICC. This PRG signature not only reflects the TME immune status but also provides new biomarkers for ICC prognosis.