{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319631/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319631"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Secretome analysis during human induced pluripotent stem cell-derived cardiomyocyte differentiation","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":"GSE319631","cross_references":{"GSM":["GSM9521819","GSM9521815","GSM9521816","GSM9521817","GSM9521818","GSM9521813","GSM9521814","GSM9521820","GSM9521821"],"GPL":["24676"],"GSE":["319631"],"taxon":["Homo sapiens"],"PMID":["[42541290]"]}}