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Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study)

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Abstract

Mortality in infants with hypoplastic left heart syndrome (HLHS) is strongly correlated with right ventricle (RV) dysfunction. Cell therapy has demonstrated potential improvements of RV dysfunction in animal models related to HLHS, and neonatal human derived c-kit+ cardiac-derived progenitor cells (CPCs) show superior efficacy when compared to adult human cardiac-derived CPCs (aCPCs). Neonatal CPCs (nCPCs) have yet to be investigated in humans. The CHILD trial (Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome) is a Phase I/II trial aimed at investigating intramyocardial administration of autologous nCPCs in HLHS infants by assessing the feasibility, safety, and potential efficacy of CPC therapy. Using an open-label, multicenter design, CHILD investigates nCPC safety and feasibility in the first enrollment group (Group A/Phase I). In the second enrollment group, CHILD uses a randomized, double-blinded, multicenter design (Group B/Phase II), to assess nCPC efficacy based on RV functional and structural characteristics. The study plans to enroll 32 patients across 4 institutions: Group A will enroll 10 patients, and Group B will enroll 22 patients. CHILD will provide important insights into the therapeutic potential of nCPCs in patients with HLHS.

Clinical Trial Registration https://clinicaltrials.gov/ct2/home NCT03406884, First posted January 23, 2018.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The CHILD trial is funded through Marcus Foundation, Inc. Sunjay Kaushal is funded by grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (R01HL118491, R01 HL139060-01A1, R42HL131226-01); Moseley Foundation; and Maryland Stem Cell Research. Joshua M. Hare is funded by grants from the NIH/National Heart, Lung, and Blood Institute (R01 HL107110, 1R01HL134558-01, 4R01HL084275-10, 5R01HL116899-04, and HHSN268201600012I); NIH/National Cancer Institute (5R01CA136387-07); Soffer Foundation; and Sarr Foundation. Ming-Sing Si is funded by NIH grant K08HL146351.

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Authors and Affiliations

  1. Division of Cardiovascular-Thoracic Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Avenue, Chicago, IL, 60611, USA

    Sunjay Kaushal, Riley M. Boyd, Mohamed Abdullah, Rachana Mishra & Sudhish Sharma

  2. Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, 9th Floor, Miami, FL, 33136, USA

    Joshua M. Hare & Aisha Khan

  3. Division of Cardiac Surgery, University of Maryland School of Medicine, 110 S. Paca Street, 7th Floor, Baltimore, MD, 21228, USA

    Aakash M. Shah & Abigail Snyder

  4. Division of Pediatric Cardiology, University of Maryland School of Medicine, 110 S. Paca Street, 7th Floor, Baltimore, MD, 21228, USA

    Nicholas P. Pietris

  5. School of Public Health, UT Health, 1200 Pressler, Houston, TX, 77030, USA

    Judith L. Bettencourt, Linda B. Piller, Barry R. Davis & Dejian Lai

  6. Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, 1760 Haygood Drive W200, Atlanta, GA, 30322, USA

    Timothy C. Slesnick & Michael E. Davis

  7. University of Michigan, CS Mott Children’s Hospital, 1540 E. Hospital Drive, 11-735, Ann Arbor, MI, 48109, USA

    Ming-Sing Si

  8. Department of Cardiac Surgery, Emory University Children’s Healthcare of Atlanta, 1405 Clifton Road NE, Atlanta, GA, 30322, USA

    Paul J. Chai

  9. Division of Cardiology, Department of Pediatrics, Emory University, Children’s Healthcare of Atlanta, Atlanta, 201 Uppergate Drive, Atlanta, GA, 30322, USA

    Michael E. Davis & William T. Mahle

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  1. Sunjay Kaushal
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  2. Joshua M. Hare
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Corresponding authors

Correspondence to Sunjay Kaushal or Joshua M. Hare.

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Conflict of interest

Joshua M. Hare reports having a patent for cardiac cell-based therapy and holds equity in Vestion Inc. and maintains a professional relationship with Vestion Inc. as a consultant and member of the Board of Directors and Scientific Advisory Board. Vestion Inc. did not play a role in the design, conduct, or funding of the study. Dr. Joshua Hare is the Chief Scientific Officer, a compensated consultant and board member for Longeveron Inc. and holds equity in Longeveron. Dr. Hare is also the co-inventor of intellectual property licensed to Longeveron. Longeveron did not play a role in the design, conduct, or funding of the study. The University of Miami is an equity owner in Longeveron Inc., which has licensed intellectual property from the University of Miami. Sunjay Kaushal is a founder of Neoprogen, Inc.

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Kaushal, S., Hare, J.M., Shah, A.M. et al. Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). Pediatr Cardiol 43, 1481–1493 (2022). https://doi.org/10.1007/s00246-022-02872-6

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