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Clinical Trial
. 2025 May 1;16(1):215.
doi: 10.1186/s13287-025-04316-3.

Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections

Carlos Gallego-Navarro  1   2 , James Jaggers  3 , Harold M Burkhart  4 , Waldemar F Carlo  5 , David L Morales  6 , M Yasir Qureshi  2   7 , Joseph W Rossano  8 , Clinton E Hagen  9 , Drew K Seisler  2 , Susana Cantero Peral  1   2 , Timothy J Nelson  10   11   12   13   14
Affiliations
Clinical Trial

Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections

Carlos Gallego-Navarro et al. Stem Cell Res Ther. .

Abstract

Background: Preliminary phase I clinical trial results revealed that autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) preserved right ventricular cardiac function. To establish the efficacy of intramyocardial injections of an autologous UCB-MNC product at the time of stage II palliation surgery in patients with hypoplastic left heart syndrome (HLHS).

Methods: A phase IIb, multicenter, open-label, nonrandomized study was conducted. Ninety-five children (fifty treated and forty-five controls) with HLHS and its variants, a history of stage I palliation surgery, and planned stage II palliation surgery at less than thirteen months were enrolled. We assessed coprimary efficacy endpoints for changes in right ventricular cardiac function through fractional area changes and longitudinal and circumferential strain, both in the short term (three months) and long term (twelve months). Second, we assessed changes in biomarkers of cardiac injury. Safety endpoints included severe adverse events (SAEs), changes in overall health through vital signs, and cumulative hospitalization.

Results: Assessment of our coprimary efficacy endpoints revealed an unfavorable change in longitudinal cardiac strain in the treatment group compared with an improvement in strain in the control group (unadjusted p =.032) in the short term. No differences were observed between the groups in terms of other coprimary efficacy endpoints in the short or long term. A secondary assessment of biomarkers of cardiac injury revealed higher troponin T levels in the treatment group at three and six hours postsurgery. Regarding safety, no deaths related to the administered product or delivery procedure were reported. The treatment group presented a greater incidence (20%) of at least one SAE than the control group at three months (p =.048). Additionally, no statistically significant differences were found for the other safety endpoints.

Conclusion: Intramyocardial injections of autologous UCB-MNC products into the right ventricular myocardium during stage II palliation surgery failed to enhance cardiac function in patients with hypoplastic left heart syndrome. REGISTERED ON CLINICALTRIALS.GOV: Registered on ClinicalTrials.gov (NCT03779711) on 12/04/2018; URL: https://clinicaltrials.gov/ct2/show/NCT0377971 .

Keywords: Hypoplastic left heart syndrome; Mononuclear cells; Regenerative therapy; Single ventricle; Stem cell; Umbilical cord blood stem cell transplantation.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study titled “Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood-Derived Mononuclear Cells during Stage II Surgical Repair of Hypoplastic Left Heart Syndrome (Auto Cell-II)” was individually approved by the Institutional Review Boards (IRBs) at each participating site under protocol number CSP-4401 and IND 15343 on August 30, 2018. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Artificial intelligence: The authors declare that they have not used AI-generated work in this manuscript.

Figures

Fig. 1
Fig. 1
Consort flow diagram showing the number of enrolled subjects, subject allocation into treatment groups, and primary endpoint data available
Fig. 2
Fig. 2
Adverse event incidence within one year of enrollment by system organ
See this image and copyright information in PMC

References

    1. van der Linde D, Konings EEM, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJM et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol [Internet]. 2011;58(21):2241–7. Available from: 10.1016/j.jacc.2011.08.025 - PubMed
    1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation [Internet]. 2021;143(8):e254–743. Available from: 10.1161/CIR.0000000000000950 - PubMed
    1. De Rita F, Crossland D, Griselli M, Hasan A. Management of the failing Fontan. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu [Internet]. 2015;18(1):2–6. Available from: 10.1053/j.pcsu.2015.01.004 - PubMed
    1. Gordon BM, Rodriguez S, Lee M, Chang R-K. Decreasing number of deaths of infants with hypoplastic left heart syndrome. J Pediatr [Internet]. 2008;153(3):354–8. Available from: 10.1016/j.jpeds.2008.03.009 - PubMed
    1. Barron DJ, Kilby MD, Davies B, Wright JGC, Jones TJ, Brawn WJ. Hypoplastic left heart syndrome. Lancet [Internet]. 2009;374(9689):551–64. Available from: 10.1016/S0140-6736(09)60563-8 - PubMed

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