{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:24:43Z","timestamp":1762424683691,"version":"build-2065373602"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1186861","GNT1186861"],"award-info":[{"award-number":["GNT1186861","GNT1186861"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Letter to the editor regarding: Gallego-Navarro C, Jaggers J, Burkhart HM, Carlo WF, Morales DL, Qureshi MY, Rossano JW, Hagen CE, Seisler DK, Peral SC, Nelson TJ. Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections. Stem Cell Res Ther. 2025 May 1;16(1):215. doi:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"10.1186\/s13287-025-04316-3\" ext-link-type=\"doi\">https:\/\/doi.org\/10.1186\/s13287-025-04316-3<\/jats:ext-link>\n                    . This phase IIb clinical cell therapy trial with autologous cord blood mononuclear cells is notable and highly commended as an important effort in very challenging clinical conditions in which new cell treatment advancements have been limited. In light of their findings of unfavourable clinical findings, our letter highlights that their study is intertwined with the complexity of the clinical pathology within immature pediatric hearts, cardiac surgical intervention strategy and other related study design hurdles. These difficulties contribute to confound the interpretation of cell treatment efficacy and clinical safety. Based on this study and our own recent clinical study, we make a call for future studies testing cell therapy in the congenital heart disease setting, to implement far greater consideration of the mode and timing of cell delivery and congruency with myocardial tissue remodelling and developmental growth processes in small hearts.\n                  <\/jats:p>","DOI":"10.1186\/s13287-025-04717-4","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:19:38Z","timestamp":1762424378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjunct cell therapy for hypoplastic left heart syndrome: therapeutic promise requires targeted design strategy"],"prefix":"10.1186","volume":"16","author":[{"given":"Christian P.","family":"Brizard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5547-0232","authenticated-orcid":false,"given":"Salvatore","family":"Pepe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"issue":"1","key":"4717_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s13287-025-04316-3","volume":"16","author":"C Gallego-Navarro","year":"2025","unstructured":"Gallego-Navarro C, Jaggers J, Burkhart HM, Carlo WF, Morales DL, Qureshi MY, Rossano JW, Hagen CE, Seisler DK, Peral SC, Nelson TJ. Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections. Stem Cell Res Ther. 2025;16(1):215. https:\/\/doi.org\/10.1186\/s13287-025-04316-3.","journal-title":"Stem Cell Res Ther"},{"issue":"6","key":"4717_CR2","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1016\/j.jtcvs.2023.07.035","volume":"166","author":"CP Brizard","year":"2023","unstructured":"Brizard CP, Elwood NJ, Kowalski R, Horton SB, Jones BO, Hutchinson D, Zannino D, Sheridan BJ, Butt W, Cheung MMH, Pepe S. Safety and feasibility of adjunct autologous cord blood stem cell therapy during the Norwood heart operation. J Thorac Cardiovasc Surg. 2023;166(6):1746\u201355. https:\/\/doi.org\/10.1016\/j.jtcvs.2023.07.035.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"4717_CR3","unstructured":"NetCord-FACT (Foundation for the Accreditation of Cell Therapy). International standards for cord blood Collection, Banking, and release for administration (Version 8). https:\/\/www.factglobal.org\/standards\/cbb-standards\/ Accessed 29 Jul 2025."},{"issue":"3","key":"4717_CR4","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.athoracsur.2015.04.130","volume":"100","author":"CP Brizard","year":"2015","unstructured":"Brizard CP, Looi JY, Smolich JJ, Horton SB, Angerosa J, Elwood NJ, Pepe S. Safety of intracoronary human cord blood stem cells in a lamb model of infant cardiopulmonary bypass. Ann Thorac Surg. 2015;100(3):1021\u20139. https:\/\/doi.org\/10.1016\/j.athoracsur.2015.04.130.","journal-title":"Ann Thorac Surg"},{"key":"4717_CR5","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1097\/CD9.0000000000000028","volume":"1","author":"AM Gerdes","year":"2021","unstructured":"Gerdes AM. When does the human heart transition from hyperplastic myocyte growth to myocyte hypertrophy? Cardiol Discovery. 2021;1:202\u20133.","journal-title":"Cardiol Discovery"},{"issue":"2","key":"4717_CR6","doi-asserted-by":"publisher","first-page":"e017839","DOI":"10.1161\/JAHA.120.017839","volume":"10","author":"SP Bishop","year":"2021","unstructured":"Bishop SP, Zhou Y, Nakada Y, Zhang J. Changes in cardiomyocyte cell cycle and hypertrophic growth during fetal to adult in mammals. J Am Heart Assoc. 2021;10(2):e017839. https:\/\/doi.org\/10.1161\/JAHA.120.017839.","journal-title":"J Am Heart Assoc"},{"issue":"1","key":"4717_CR7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1136\/heartjnl-2015-308348","volume":"102","author":"D Iacobazzi","year":"2016","unstructured":"Iacobazzi D, Suleiman MS, Ghorbel M, George SJ, Caputo M, Tulloh RM. Cellular and molecular basis of RV hypertrophy in congenital heart disease. Heart. 2016;102(1):12\u20137. https:\/\/doi.org\/10.1136\/heartjnl-2015-308348.","journal-title":"Heart"},{"key":"4717_CR8","doi-asserted-by":"publisher","first-page":"1981568","DOI":"10.1155\/2018\/1981568","volume":"2018","author":"S Guimaron","year":"2018","unstructured":"Guimaron S, Guihaire J, Amsallem M, Haddad F, Fadel E, Mercier O. Current knowledge and recent advances of right ventricular molecular biology and metabolism from congenital heart disease to chronic pulmonary hypertension. Biomed Res Int. 2018;2018:1981568. https:\/\/doi.org\/10.1155\/2018\/1981568.","journal-title":"Biomed Res Int"},{"issue":"5","key":"4717_CR9","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1016\/j.jtcvs.2017.12.042","volume":"155","author":"ME Bowen","year":"2018","unstructured":"Bowen ME, Liu X, Sundwall PM, Drakos SG, Li DY, Selzman CH, McKellar SH. Right ventricular involution: what can we learn from nature\u2019s model of compensated hypertrophy? J Thorac Cardiovasc Surg. 2018;155(5):2024\u2013e20281. https:\/\/doi.org\/10.1016\/j.jtcvs.2017.12.042.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"4717_CR10","doi-asserted-by":"publisher","first-page":"e038137","DOI":"10.1161\/JAHA.124.038137","volume":"13","author":"K Hirai","year":"2024","unstructured":"Hirai K, Sawada R, Hayashi T, Araki T, Nakagawa N, Kondo M, Yasuda K, Hirata T, Sato T, Nakatsuka Y, Yoshida M, Kasahara S, Baba K, Oh H, TICAP\/PERSEUS Study Group. Eight-year outcomes of cardiosphere-derived cells in single ventricle congenital heart disease. J Am Heart Assoc. 2024;13:e038137. https:\/\/doi.org\/10.1161\/JAHA.124.038137.","journal-title":"J Am Heart Assoc"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04717-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04717-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04717-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:19:41Z","timestamp":1762424381000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04717-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4717"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04717-4","relation":{},"ISSN":["1757-6512"],"issn-type":[{"type":"electronic","value":"1757-6512"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"6 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"620"}}