Dataset Information

Protective effects on melphalan-induced mouse intestinal injury treated by Human Umbilical Cord-derived Mesenchymal Stem Cells

ABSTRACT: Autologous peripheral hematopoietic stem cell transplantation (autoHSCT) is one front-line therapy with high-dose melphalan for multiple myeloma (MM). Patients with MM who receive conditioning regimen with melphalan usually suffer from severe gastrointestinal symptoms, as one of nonhematological toxicities. Aim: It is an urgent demand to develop an effective methods to repair the intestinal injuries in patients with MM receiving conditioning regimen with high-dose melphalan for autoHSCT. Therefore, the protective effects of Human umbilical cord derived-mesenchymal stem cells (hucMSCs) is investigated after infusion into mouse model with melphalan-induce gastrointestinal injuries.

ORGANISM(S): Mus musculus

PROVIDER: GSE225899 | GEO | 2024/04/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. Methods and Findings Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5–6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups. Conclusions Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity

Project description:Purpose: Evaluate the molecular changes associated with melphalan-induced cardiotoxicity and rescue by N-acetyl-L-cysteine (NAC) supplementation. Methods: RNA-Seq analysis was performed to analyze global transcriptome profiles of hiPSC-CMs treated with DMSO (Control group), 20 µM melphalan (Mel group), and 20 µM melphalan with 1 mM NAC (Mel+NAC group), respectively. The Illumina TruSeq technology was used to prepare RNA-Seq libraries, and next-generation sequencing was done via an Illumina HWI-ST1276. RNA sequence reads were aligned to the human reference genome (GRCh38) using STAR v2.5. HTSeq v0.6.1 was used to count the read numbers mapped of each gene, and then Fragments Per Kilobase Million (FPKM) was calculated to estimate gene abundance. Differential expression analysis was performed using the DESeq2 R package (2_1.6.3). The resulting P-values were adjusted using the Benjamini and Hochberg's approach. Results: As detected by RNA-Seq, more genes were down-regulated than up-regulated by the treatment of melphalan, whereas NAC supplementation resulted in more genes being up-regulated than down-regulated. Among the top 10 up-regulated genes by melphalan treatment, 4 were direct p53 effectors (CDKN1A, EDXR, TNFRSF10C, and GDF15). And among the top 10 down-regulated genes by melphalan treatment, 5 were correlated to cell adhesion (CDH13, CNTN1, SDK1, CTNND2, and PARD3B). In addition, the up- and down-regulation of genes involved in oxidative stress (e.g., DUOX2 and NOX4) following melphalan treatment (Mel vs. control) was attenuated with NAC supplementation (Mel+NAC vs. Control). Similarly, the up- and down-regulation of genes involved in cardiac muscle contraction (e.g., Ca2+ handling proteins CACNA1C, RYR2 and CASQ2 and cardiac contractile proteins TNNC1, ACTC1, TNNC1) and cardiac conduction (e.g., ATP2B2 and ABCC9) following melphalan treatment (Mel vs. Control) was attenuated with NAC supplementation (Mel+NAC vs. Control). Conclusion: NAC ameliorates melphalan-induced alteration of hiPSC-CM transcriptomic profiles.

Dataset Information

Protective effects on melphalan-induced mouse intestinal injury treated by Human Umbilical Cord-derived Mesenchymal Stem Cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets