Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities
Sara Azhari Mohamed, Linda Howard, Veronica McInerney, Amjad Hayat, Janusz Krawczyk, Sean Naughton, Andrew Finnerty, Miriam Holohan, Aoife Duffy, Tony Moloney, Eamon Kavanagh, Paul Burke, Aaron Liew, Muhammad Tubassam, Stewart Redmond Walsh, Timothy O'Brien, Sara Azhari Mohamed, Linda Howard, Veronica McInerney, Amjad Hayat, Janusz Krawczyk, Sean Naughton, Andrew Finnerty, Miriam Holohan, Aoife Duffy, Tony Moloney, Eamon Kavanagh, Paul Burke, Aaron Liew, Muhammad Tubassam, Stewart Redmond Walsh, Timothy O'Brien
Abstract
Background: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI.
Methods: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs.
Results: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy.
Conclusions: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.
Keywords: abnormal karyotype; chronic limb-threatening ischemia; critical limb ischemia; mesenchymal stromal cells; phase 1 clinical trial.
Copyright © 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.
Source: PubMed