Follow-up of intramyocardial bone marrow mononuclear cell transplantation beyond 10 years.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
14 Feb 2024
Historique:
received: 19 07 2023
accepted: 05 02 2024
medline: 15 2 2024
pubmed: 15 2 2024
entrez: 15 2 2024
Statut: epublish

Résumé

Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.

Identifiants

pubmed: 38355940
doi: 10.1038/s41598-024-53776-9
pii: 10.1038/s41598-024-53776-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3747

Subventions

Organisme : Finnish government subsidies for medical research block grants-awarded funding
ID : TYH2021346

Investigateurs

Pekka Hämmäinen (P)
Jukka Schildt (J)
Aapo Ahonen (A)
Päivi Nikkinen (P)
Anne Nihtinen (A)
Riitta Alitalo (R)
Reino Pöyhiä (R)

Informations de copyright

© 2024. The Author(s).

Références

Dai, W. & Kloner, R. A. Bone marrow-derived cell transplantation therapy for myocardial infarction: Lessons learned and future questions. Am. J. Transpl. 11, 2297–2301. https://doi.org/10.1111/j.1600-6143.2011.03750.x (2011).
doi: 10.1111/j.1600-6143.2011.03750.x
Patila, T. et al. Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass. J. Heart Lung Transpl. 33, 567–574. https://doi.org/10.1016/j.healun.2014.02.009 (2014).
doi: 10.1016/j.healun.2014.02.009
Lehtinen, M. et al. Intramyocardial bone marrow mononuclear cell transplantation in ischemic heart failure: Long-term follow-up. J. Heart Lung Transpl. 34, 899–905. https://doi.org/10.1016/j.healun.2015.01.989 (2015).
doi: 10.1016/j.healun.2015.01.989
Afzal, M. R. et al. Adult bone marrow cell therapy for ischemic heart disease. Circ. Res. 117, 558–575. https://doi.org/10.1161/CIRCRESAHA.114.304792 (2015).
doi: 10.1161/CIRCRESAHA.114.304792 pubmed: 26160853 pmcid: 4553075
Bolli, R., Solankhi, M., Tang, X. L. & Kahlon, A. Cell therapy in patients with heart failure: A comprehensive review and emerging concepts. Cardiovasc. Res. 118, 951–976. https://doi.org/10.1093/cvr/cvab135 (2022).
doi: 10.1093/cvr/cvab135 pubmed: 33871588
Fisher, S. A. et al. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD007888.pub2 (2014).
doi: 10.1002/14651858.CD007888.pub2 pubmed: 25248140 pmcid: 5886855
Fisher, S. A., Doree, C., Mathur, A., Taggart, D. P. & Martin-Rendon, E. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst. Rev. 12, CD007888. https://doi.org/10.1002/14651858.CD007888.pub3 (2016).
doi: 10.1002/14651858.CD007888.pub3 pubmed: 28012165
Fisher, S. A., Doree, C., Mathur, A., Taggart, D. P. & Martin-Rendon, E. Cochrane Corner: stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Heart 104, 8–10. https://doi.org/10.1136/heartjnl-2017-311684 (2018).
doi: 10.1136/heartjnl-2017-311684 pubmed: 28607164
Wang, Y. et al. Effect of stem cell transplantation on patients with ischemic heart failure: A systematic review and meta-analysis of randomized controlled trials. Stem Cell Res. Ther. 10, 125. https://doi.org/10.1186/s13287-019-1214-0 (2019).
doi: 10.1186/s13287-019-1214-0 pubmed: 30999928 pmcid: 6472092
Lee, S. H., Hong, J. H., Cho, K. H., Noh, J.-W. & Cho, H.-J. Discrepancy between short-term and long-term effects of bone marrow-derived cell therapy in acute myocardial infarction: A systematic review and meta-analysis. Stem Cell Res. Therapy 7, 153. https://doi.org/10.1186/s13287-016-0415-z (2016).
doi: 10.1186/s13287-016-0415-z
Lehtinen, M. et al. Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery: Perioperative safety study. Interact Cardiovasc. Thorac. Surg. 19, 990–996. https://doi.org/10.1093/icvts/ivu265 (2014).
doi: 10.1093/icvts/ivu265 pubmed: 25142068
Cerqueira, M. D. et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105, 539–542. https://doi.org/10.1161/hc0402.102975 (2002).
doi: 10.1161/hc0402.102975 pubmed: 11815441
Wang, R. et al. Long-term outcome of intra-myocardial injection of autologous bone marrow mononuclear cells combined with isolated coronary artery bypass grafting for patients with chronic ischemic heart failure. Heart Surg. Forum 19, E131-138. https://doi.org/10.1532/hsf.1505 (2016).
doi: 10.1532/hsf.1505 pubmed: 27355149
Völz, S. et al. Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: Insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Eur. Heart J. 42, 2657–2664. https://doi.org/10.1093/eurheartj/ehab273 (2021).
doi: 10.1093/eurheartj/ehab273 pubmed: 34023903 pmcid: 8282315
Pandozi, C. et al. The scar: The wind in the perfect storm-insights into the mysterious living tissue originating ventricular arrhythmias. J. Interv. Card Electrophysiol. https://doi.org/10.1007/s10840-021-01104-w (2022).
doi: 10.1007/s10840-021-01104-w pubmed: 35322330 pmcid: 9931863
de Haan, S. et al. Scar size and characteristics assessed by CMR predict ventricular arrhythmias in ischaemic cardiomyopathy: Comparison of previously validated models. Heart 97, 1951–1956. https://doi.org/10.1136/heartjnl-2011-300060 (2011).
doi: 10.1136/heartjnl-2011-300060 pubmed: 21917670
Gulati, A. et al. Absence of myocardial fibrosis predicts favorable long-term survival in new-onset heart failure. Circ. Cardiovasc. Imag. 11, e007722. https://doi.org/10.1161/circimaging.118.007722 (2018).
doi: 10.1161/circimaging.118.007722
Banovic, M. et al. Endpoints in stem cell trials in ischemic heart failure. Stem Cell Res. Ther. 6, 159. https://doi.org/10.1186/s13287-015-0143-9 (2015).
doi: 10.1186/s13287-015-0143-9 pubmed: 26319401 pmcid: 4552990
Sanganalmath, S. K. & Bolli, R. Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ. Res. 113, 810–834. https://doi.org/10.1161/circresaha.113.300219 (2013).
doi: 10.1161/circresaha.113.300219 pubmed: 23989721 pmcid: 3892665
Hosseinpour, A., Kheshti, F., Kazemi, A. & Attar, A. Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: A meta-analysis of clinical trials. Stem Cell Res. Therapy 13, 203. https://doi.org/10.1186/s13287-022-02883-3 (2022).
doi: 10.1186/s13287-022-02883-3
Yang, Y. J. et al. Strengthening effects of bone marrow mononuclear cells with intensive atorvastatin in acute myocardial infarction. Open Heart https://doi.org/10.1136/openhrt-2019-001139 (2020).
doi: 10.1136/openhrt-2019-001139 pubmed: 33046592 pmcid: 7552833

Auteurs

Severi Mulari (S)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Faculty of Medicine, Department of Pharmacology, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.

Risto Kesävuori (R)

Department of Radiology, HUS Medical Imaging Center and Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Juhani A Stewart (JA)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Pasi Karjalainen (P)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Miia Holmström (M)

Department of Radiology, HUS Medical Imaging Center and Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Miia Lehtinen (M)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Juha Peltonen (J)

Department of Radiology, HUS Medical Imaging Center and Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Mika Laine (M)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Juha Sinisalo (J)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Tatu Juvonen (T)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Markku Kupari (M)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Ari Harjula (A)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Tommi Pätilä (T)

Pediatric Cardiac Surgery, Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Sari Kivistö (S)

Department of Radiology, HUS Medical Imaging Center and Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Esko Kankuri (E)

Faculty of Medicine, Department of Pharmacology, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland. esko.kankuri@helsinki.fi.

Antti Vento (A)

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Classifications MeSH