{"doi":"10.1007/s10456-024-09929-5","title":"Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Coronary microvascular disease (CMD) and its progression towards major adverse coronary events pose a significant health challenge. Accurate in vitro investigation of CMD requires a robust cell model that faithfully represents the cells within the cardiac microvasculature. Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) offer great potential; however, they are traditionally derived via differentiation protocols that are not readily scalable and are not specified towards the microvasculature. Here, we report the development and comprehensive characterisation of a scalable 3D protocol enabling the generation of phenotypically stable cardiac hPSC-microvascular-like ECs (hPSC-CMVECs) and cardiac pericyte-like cells. These were derived by growing vascular organoids within 3D stirred tank bioreactors and subjecting the emerging 3D hPSC-ECs to high-concentration VEGF-A treatment (3DV). Not only did this promote phenotypic stability of the 3DV hPSC-ECs; single cell-RNA sequencing (scRNA-seq) revealed the pronounced expression of cardiac endothelial- and microvascular-associated genes. Further, the generated mural cells attained from the vascular organoid exhibited markers characteristic of cardiac pericytes. Thus, we present a suitable cell model for investigating the cardiac microvasculature as well as the endothelial-dependent and -independent mechanisms of CMD. Moreover, owing to their phenotypic stability, cardiac specificity, and high angiogenic potential, the cells described within would also be well suited for cardiac tissue engineering applications.</jats:p>","journal":"Angiogenesis","year":2024,"id":629044,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1628974,"name":"Bishwa R. Ghimire","orcid":null,"position":1,"is_corresponding":false},{"id":50059,"name":"Bela Merkely","orcid":null,"position":2,"is_corresponding":false},{"id":1063483,"name":"Anna M. Randi","orcid":"0000-0002-0729-211X","position":3,"is_corresponding":false},{"id":1628976,"name":"Sian E. Harding","orcid":null,"position":4,"is_corresponding":false},{"id":1296158,"name":"Virpi Talman","orcid":"0000-0002-2702-6505","position":5,"is_corresponding":false},{"id":794104,"name":"Gábor Földes","orcid":"0000-0003-4415-352X","position":6,"is_corresponding":false},{"id":1628973,"name":"Qasim A. Majid","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Coronary microvascular disease (CMD) and its progression towards major adverse coronary events pose a significant health challenge. Accurate in vitro investigation of CMD requires a robust cell model that faithfully represents the cells within the cardiac microvasculature. Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) offer great potential; however, they are traditionally derived via differentiation protocols that are not readily scalable and are not specified towards the microvasculature. Here, we report the development and comprehensive characterisation of a scalable 3D protocol enabling the generation of phenotypically stable cardiac hPSC-microvascular-like ECs (hPSC-CMVECs) and cardiac pericyte-like cells. These were derived by growing vascular organoids within 3D stirred tank bioreactors and subjecting the emerging 3D hPSC-ECs to high-concentration VEGF-A treatment (3DV). Not only did this promote phenotypic stability of the 3DV hPSC-ECs; single cell-RNA sequencing (scRNA-seq) revealed the pronounced expression of cardiac endothelial- and microvascular-associated genes. Further, the generated mural cells attained from the vascular organoid exhibited markers characteristic of cardiac pericytes. Thus, we present a suitable cell model for investigating the cardiac microvasculature as well as the endothelial-dependent and -independent mechanisms of CMD. Moreover, owing to their phenotypic stability, cardiac specificity, and high angiogenic potential, the cells described within would also be well suited for cardiac tissue engineering applications.</jats:p>","is_dataset_classified":null,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38775849","pmcid":"PMC11303486","openalex_id":"https://openalex.org/W4398204502","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"MR/R025002/1","title":"Vascular constructs using human pluripotent stem cells in the therapy of peripheral arterial disease"},{"funder_name":"British Heart Foundation","grant_id":"RE/13/4/30184","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_19040","title":null},{"funder_name":"British Heart Foundation","grant_id":"RM/17/1/33377","title":null},{"funder_name":"Semmelweis University","grant_id":"","title":null}],"total_grants":5,"fwci":2.793,"citation_percentile":0.91298759,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":14},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s10456-024-09929-5.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s10456-024-09929-5.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s10456-024-09929-5/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10456-024-09929-5","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38775849","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11303486","host_type":"repository"},{"url":"https://www.utupub.fi/handle/10024/189255","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11303486","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11303486?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.21203/rs.3.rs-3759468/v1","host_type":""},{"url":"http://dx.doi.org/10.1007/s10456-024-09929-5","host_type":""},{"url":"http://hdl.handle.net/10138/595466","host_type":""}],"fields_of_study":["Congenital heart defects research","Pluripotent Stem Cells Research","Tissue Engineering and Regenerative Medicine","0303 health sciences","03 medical and health sciences","Humans","Pluripotent Stem Cells","Endothelial Cells","Microvessels","Cell Differentiation","Pericytes","Vascular Endothelial Growth Factor A","Organoids"],"mesh_terms":["Cell Differentiation","Humans","Organoids","Pericytes","Pluripotent Stem Cells","Vascular Endothelial Growth Factor A","Endothelial Cells","Microvessels"],"keywords":["Induced pluripotent stem cell","Angiogenesis","Endothelial stem cell","Cell biology","Human Induced Pluripotent Stem Cells","Stem cell","Computational biology","Biology","Cancer research","Embryonic stem cell","Biochemistry","Microvascular Endothelial cells","3D Cell Culture","Endothelial To Mesenchymal Transition","Vascular Organoids","Cardiac Microvascular Disease","Human Pluripotent Stem Cell (Hpsc)-derived Endothelial Cells","Pluripotent Stem Cells","Vascular Endothelial Growth Factor A","Original Paper","Endothelial Cells","Cell Differentiation","Pharmacy","Organoids","Microvessels","Humans","Pericytes"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T16:13:29.447153Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}