TY - JOUR
T1 - Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome
T2 - The ELPIS phase i trial
AU - Kaushal, Sunjay
AU - Hare, Joshua M.
AU - Hoffman, Jessica R.
AU - Boyd, Riley M.
AU - Ramdas, Kevin N.
AU - Pietris, Nicholas
AU - Kutty, Shelby
AU - Tweddell, James S.
AU - Husain, S. Adil
AU - Menon, Shaji C.
AU - Lambert, Linda M.
AU - Danford, David A.
AU - Kligerman, Seth J.
AU - Hibino, Narutoshi
AU - Korutla, Laxminarayana
AU - Vallabhajosyula, Prashanth
AU - Campbell, Michael J.
AU - Khan, Aisha
AU - Naioti, Eric
AU - Yousefi, Keyvan
AU - Mehranfard, Danial
AU - McClain-Moss, Lisa
AU - Oliva, Anthony A.
AU - Davis, Michael E.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-Treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-Treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway. Trial registration number NCT03525418.
AB - Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-Treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-Treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway. Trial registration number NCT03525418.
KW - allogeneic medicinal signalling cells
KW - Hypoplastic left heart syndrome
KW - Lomecel-B
KW - mesenchymal stem cells
KW - mesenchymal stromal cells
UR - https://www.scopus.com/pages/publications/85152677125
UR - https://www.scopus.com/inward/citedby.url?scp=85152677125&partnerID=8YFLogxK
U2 - 10.1093/ehjopen/oead002
DO - 10.1093/ehjopen/oead002
M3 - Article
AN - SCOPUS:85152677125
SN - 2752-4191
VL - 3
JO - European Heart Journal Open
JF - European Heart Journal Open
IS - 2
M1 - oead002
ER -