In Vivo MRI Tracking of Mesenchymal Stromal Cells Labeled with Ultrasmall Paramagnetic Iron Oxide Particles after Intramyocardial Transplantation in Patients with Chronic Ischemic Heart Disease
Open Access
- 14 November 2019
- journal article
- research article
- Published by Hindawi Limited in Stem Cells International
- Vol. 2019, 1-10
- https://doi.org/10.1155/2019/2754927
Abstract
Background. While regenerative stem cell therapy for ischemic heart disease has moved into phase 3 studies, little is still known about retention and migration of cell posttransplantation. In human studies, the ability to track transplanted cells has been limited to labeling with radioisotopes and tracking using nuclear imaging. This method is limited by low resolution and short half-lives of available radioisotopes. Longitudinal tracking using magnetic resonance imaging (MRI) of myocardial injected cells labeled with iron oxide nanoparticles has shown promising results in numerous preclinical studies but has yet to be evaluated in human studies. We aimed to evaluate MRI tracking of mesenchymal stromal cells (MSCs) labeled with ultrasmall paramagnetic iron oxide (USPIO) nanoparticles after intramyocardial transplantation in patients with ischemic heart disease (IHD). Methods. Five no-option patients with chronic symptomatic IHD underwent NOGA-guided intramyocardial transplantation of USPIO-labeled MSCs. Serial MRI scans were performed to track labeled cells both visually and using semiautomated T2 relaxation time analysis. For safety, we followed symptoms, quality of life, and myocardial function for 6 months. Results. USPIO-labeled MSCs were tracked for up to 14 days after transplantation at injection sites both visually and using semiautomated regional T2 relaxation time analysis. Labeling of MSCs did not impair long-term safety of treatment. Conclusion. This was a first-in-man clinical experience aimed at evaluating the utility of MRI tracking of USPIO-labeled bone marrow-derived autologous MSCs after intramyocardial injection in patients with chronic IHD. The treatment was safe, and cells were detectable at injection sites up to 14 days after transplantation. Further studies are needed to clarify if MSCs migrate out of the injection area into other areas of the myocardium or if injected cells are washed out into the peripheral circulation. The trial is registered with ClinicalTrials.gov NCT03651791.Funding Information
- Agency for Science, Technology and Research
This publication has 46 references indexed in Scilit:
- A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Nonischemic Heart FailureCirculation Research, 2015
- Mesenchymal Stromal Cell Phenotype is not Influenced by Confluence during Culture ExpansionStem Cell Reviews and Reports, 2012
- Effect of transplantation with autologous bone marrow stem cells on acute myocardial infarctionInternational Journal of Cardiology, 2011
- Bone Marrow Mesenchymal Stem Cells Stimulate Cardiac Stem Cell Proliferation and DifferentiationCirculation Research, 2010
- Noninvasive Tracking of Cardiac Embryonic Stem Cells In Vivo Using Magnetic Resonance Imaging TechniquesThe International Journal of Cell Cloning, 2007
- Magnetic Resonance Tracking of Magnetically Labeled Autologous Bone Marrow CD34+ Cells Transplanted into the Spinal Cord via Lumbar Puncture Technique in Patients with Chronic Spinal Cord Injury: CD34+ Cells' Migration into the Injured SiteStem Cells and Development, 2007
- Inflammatory Response After Ischemic StrokeStroke, 2007
- Tracking Neural Stem Cells in Patients with Brain TraumaThe New England Journal of Medicine, 2006
- Iron Particles for Noninvasive Monitoring of Bone Marrow Stromal Cell Engraftment into, and Isolation of Viable Engrafted Donor Cells from, the HeartThe International Journal of Cell Cloning, 2006
- Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapyNature Biotechnology, 2005