{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319632/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Non-coding RNA profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319632"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Secretome analysis during human induced pluripotent stem cell-derived cardiomyocyte differentiation [miRNA-Seq]","description":"Introduction: Cell transplantation therapy using human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) is a promising treatment for ischemic heart disease. While paracrine effects mediated by the secretome are recognized as a key therapeutic mechanism, the dynamic changes in the secretome profile during the manufacturing process remain poorly understood. This study aimed to comprehensively elucidate the secretome dynamics of clinical-grade hiPSC-CM to identify their \"Mode of Action\" (MoA) and candidate quality attributes (CQAs). Methods: We integrated multi-omics profiling-including total RNA-seq, proteome analysis, and extracellular vesicle (EV)-derived miRNA-seq-with functional assays (proliferation, cell migration, and tube formation) using samples obtained across time points of the hiPSC-CM manufacturing process (Day 4-25). Results: High-purity hiPSC-CM (>95% cTnT positive) exhibited a distinct transcriptomic maturation between Day 16 and Day 25, characterized by the upregulation of cardiac maker genes. Proteomic clustering revealed four distinct stages, showing a functional transition from proliferation-centric signaling to tissue-repair signaling. Notably, the purified Day 25 secretome showed a qualitative shift toward a PDGF and SDF-1 rich profile. Simultaneously, EVs from Day 25 were enriched with \"myomiRs\" (miR-133b, -208b, -499b) and multiple anti-proliferative miRNAs (let-7e-5p, miR-145-5p). Functionally, the Day 25 secretome significantly enhanced mesenchymal stem/stromal cell (MSC) migration and promoted mature, highly branched endothelial tube formation compared to earlier stages. Conclusions: The hiPSC-CM secretome undergoes a programmed evolution during manufacturing, shifting from promoting undifferentiated growth to orchestrating complex tissue repair through stable angiogenesis and MSC recruitment. These findings establish a molecular foundation for the MoA of hiPSC-CM therapy and provide critical CQAs for ensuring the potency and consistency of clinical-grade cardiac products.","dates":{"publication":"2026/07/24"},"accession":"GSE319632","cross_references":{"GSM":["GSM9521826","GSM9521827","GSM9521828","GSM9521829","GSM9521822","GSM9521823","GSM9521824","GSM9521825","GSM9521830"],"GPL":["24676"],"GSE":["319632"],"taxon":["Homo sapiens"]}}