Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction

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., 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., , # 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 heat...