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Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy: The POSEIDON Randomized Trial
Study Questions:
How safe are allogeneic mesenchymal stem cells (MSCs), compared to autologous MSCs, for treatment of patients with left ventricular (LV) dysfunction due to ischemic cardiomyopathy (ICM)?
Methods:
A total of 30 patients with LV dysfunction were randomized to receive autologous or allogeneic MSCs at various doses (20, 100, or 200 million cells) by transendocardial stem cell injection into 10 LV sites. Outcome measures included serious adverse events (SAEs), 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, LV ejection fraction, early enhancement defect (EED; infarct size), and sphericity index.
Results:
The 1-year SAE incidence was 33.3% (n = 5) in the allogeneic group, and 53.3% (n = 8) in the autologous group (p = 0.46). There were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with four patients (26.7%) in the autologous group (p = 0.10). Autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (p < 0.001) and sphericity index, but did not increase ejection fraction. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced the greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.
Conclusions:
Transendocardial injection of allogeneic and autologous MSCs were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.
Perspective:
The use of allogeneic MSCs would be highly advantageous over autologous MSCs because they could be readily applied without the prerequisite for bone marrow aspiration and culture from the patient. Allogeneic MSCs might also be more functional than those cultured from an ill patient; however, they may be cleared faster due to alloreactive antibodies. Although this study is small and lacks a placebo group, results indicate that allogeneic MSCs might be safe and should be studied further. The big question remains as to whether any type of cell-based therapy targeted to improve ischemic LV dysfunction leads to meaningful improvement in outcomes.
Keywords: Myocardial Ischemia, Minnesota, Cell- and Tissue-Based Therapy, Heart Diseases, Spleen, Bone Marrow, Mesenchymal Stem Cells, Quality of Life, Cardiomyopathies, Ventricular Remodeling, Heart Failure, Mesenchymal Stem Cell Transplantation, Ventricular Dysfunction, Left, Exercise Test
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