{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/333490"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/333490","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Cellular therapy for chronic heart failure: a key role for epicardial fibronectin","abstract":"Myocardial infarction (MI) results in permanent cardiomyocyte loss, frequently leading to heart failure, with a 50% 5-year mortality. At subacute time points following MI, animal studies have shown ‘remuscularization’ of the damaged heart with human embryonic stem cell (hESC)-derived cardiomyocytes. Recently, outcomes were improved by co-delivering hESC-derived epicardium. Clinically, the main challenge remains chronic heart failure. However, hESC-cardiomyocytes alone, in the chronically infarcted heart, have shown no benefit. Here, we show that both species-matched cellular therapy and combination therapy with hESC-epicardium could attenuate cardiac dysfunction in the chronically failing heart, underpinned by sizeable cardiac grafts, cardiomyocyte proliferation and maturation, together with a host-derived vascular supply. Notably, hESC-epicardium’s augmentation of cardiomyocyte maturation within 3D-engineered heart tissues in vitro appeared to be underpinned by epicardial-secreted fibronectin. Thus, hESC-combination cell therapy holds clinical promise for ‘remuscularising’ chronically infarcted hearts.","abstract_html":"Myocardial infarction (MI) results in permanent cardiomyocyte loss, frequently leading to heart failure, with a 50% 5-year mortality. At subacute time points following MI, animal studies have shown ‘remuscularization’ of the damaged heart with human embryonic stem cell (hESC)-derived cardiomyocytes. Recently, outcomes were improved by co-delivering hESC-derived epicardium. Clinically, the main challenge remains chronic heart failure. However, hESC-cardiomyocytes alone, in the chronically infarcted heart, have shown no benefit. Here, we show that both species-matched cellular therapy and combination therapy with hESC-epicardium could attenuate cardiac dysfunction in the chronically failing heart, underpinned by sizeable cardiac grafts, cardiomyocyte proliferation and maturation, together with a host-derived vascular supply. Notably, hESC-epicardium’s augmentation of cardiomyocyte maturation within 3D-engineered heart tissues in vitro appeared to be underpinned by epicardial-secreted fibronectin. Thus, hESC-combination cell therapy holds clinical promise for ‘remuscularising’ chronically infarcted hearts.","abstract_has_math":false,"creators":["Ong, Lay Ping"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Sinha, Sanjay"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-02-20","date_published":"2021-02-20","updated_at":"2026-07-22T22:24:11Z","subjects":["cardiac regeneration","epicardium","human embryonic stem cells-derived cardiomyocytes","heart failure"],"languages":["eng"],"rights":[],"rights_urls":["https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.80910","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Sinha, Sanjay"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Wellcome Trust, Addenbrooke's Charitable Trust"]},{"key":"dc:creator","label":"Author","values":["Ong, Lay Ping"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2021-02-20"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/333490"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cardiac regeneration","epicardium","human embryonic stem cells-derived cardiomyocytes","heart failure"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.80910"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/423f08d8-3c73-4953-a1ab-16ecb5ebc468/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Myocardial infarction (MI) results in permanent cardiomyocyte loss, frequently leading to heart failure, with a 50% 5-year mortality. 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Thus, hESC-combination cell therapy holds clinical promise for ‘remuscularising’ chronically infarcted hearts."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["9b826801001c260867a1e2c67a38e9c9"]},{"key":"dc:title","label":"Title","values":["Cellular therapy for chronic heart failure: a key role for epicardial fibronectin"]}]}],"canonical_facts":{"dc:contributor.advisor":["Sinha, Sanjay"],"dc:contributor.sponsor":["Wellcome Trust, Addenbrooke's Charitable Trust"],"dc:creator":["Ong, Lay Ping"],"dc:date.issued":["2021-02-20"],"dc:description.abstract":["Myocardial infarction (MI) results in permanent cardiomyocyte loss, frequently leading to heart failure, with a 50% 5-year mortality. At subacute time points following MI, animal studies have shown ‘remuscularization’ of the damaged heart with human embryonic stem cell (hESC)-derived cardiomyocytes. Recently, outcomes were improved by co-delivering hESC-derived epicardium. Clinically, the main challenge remains chronic heart failure. However, hESC-cardiomyocytes alone, in the chronically infarcted heart, have shown no benefit. Here, we show that both species-matched cellular therapy and combination therapy with hESC-epicardium could attenuate cardiac dysfunction in the chronically failing heart, underpinned by sizeable cardiac grafts, cardiomyocyte proliferation and maturation, together with a host-derived vascular supply. Notably, hESC-epicardium’s augmentation of cardiomyocyte maturation within 3D-engineered heart tissues in vitro appeared to be underpinned by epicardial-secreted fibronectin. 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