DOI: 10.5061/dryad.tqjq2bw5b
title: Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction

description: 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.
description: 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.
description: # Intracellular delivery of nitric oxide enhances the therapeutic efficacy
 of mesenchymal stem cells for myocardial infarction
 [https://doi.org/10.5061/dryad.tqjq2bw5b](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.