Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction
Data files
Oct 23, 2023 version files 5.96 GB
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clean_data.zip
5.96 GB
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README.md
2.04 KB
Oct 23, 2023 version files 5.96 GB
-
clean_data.zip
5.96 GB
-
README.md
2 KB
Abstract
Cell therapy by autologous mesenchymal stem cells (MSCs) is a clinically acceptable strategy for treating various diseases. Unfortunately, the therapeutic efficacy is largely affected by the low quality of MSCs collected from patients. Herein, we showed that the gene expression of MSCs from patients with diabetes was differentially regulated compared to that of MSCs from healthy controls. Then, MSCs were genetically engineered to catalyse an NO prodrug to release NO intracellularly. Compared to extracellular NO conversion, intracellular NO delivery effectively prolonged survival and enhanced the paracrine function of MSCs, as demonstrated by in vitro and in vivo assays. The enhanced therapeutic efficacy of engineered MSCs combined with intracellular NO delivery was further confirmed in mouse and rat models of myocardial infarction, and a clinically relevant cell administration paradigm through secondary thoracotomy has been attempted.
README: Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction
https://doi.org/10.5061/dryad.tqjq2bw5b
RNA sequencing was performed by the BGI (Shenzhen, China). Briefly, RNA from the adipose-derived mesenchymal stem cells (ADMSCs) of healthy people and patients with diabetes was extracted using TRIzol reagent (Yeasen, China). RNA samples were sequenced on the BGISEQ platform. The raw data containing low-quality reads, adaptor sequences, and high levels of N bases were filtered before analysis. Then, the clean reads were mapped to the reference genome using HISAT, and Bowtie2 was used to align the clean reads to the reference genes. The reference genome source is NCBI, and the reference genome version is GCF_000001405.39_GRCh38.p13. The expression levels of genes were quantified to identify differentially expressed genes by RSEM. The analyses of hierarchical clustering and heatmap were performed using the online Dr. Tom system (biosys.bgi.com) to compare differential gene expression of ADMSCs in healthy people and patients with diabetes. The heatmap shows that multiple genes in MSCs from patients with diabetes were up- or downregulated compared to healthy controls. GO enrichment analysis revealed that the most differentially upregulated genes were related to TNF signalling pathways. GSEA revealed that inflammatory target genes were highly enriched in MSCs from patients with diabetes. Apoptosis-related genes were also highly enriched.Through enrichment analysis, we found that proangiogenic genes in MSCs were greatly downregulated in patients with diabetes.
Description of the data and file structure
Here are two groups of data for analysis. The Health group analyzes the adipose mesenchymal stem cells from healthy people, and the Disease group analyzes the adipose mesenchymal stem cells from diabetes patients (n=3). The data are presented in fastq format.
Methods
RNA sequencing was performed by the BGI (Shenzhen, China). Briefly, RNA from the adipose-derived mesenchymal stem cells (ADMSCs) of healthy people and patients with diabetes was extracted using TRIzol reagent (Yeasen, China). RNA samples were sequenced on the BGISEQ platform. The raw data containing low-quality reads, adaptor sequences, and high levels of N bases were filtered before analysis. Then, the clean reads were mapped to the reference genome using HISAT, and Bowtie2 was used to align the clean reads to the reference genes. The reference genome source is NCBI, and the reference genome version is GCF_000001405.39_GRCh38.p13. The expression levels of genes were quantified to identify differentially expressed genes by RSEM. The data uploaded here has not undergone any processing.