Abstract 15579: X-Ray-Visible Transmyocardial Catheter-Based Microencapsulated Mesenchymal Stem Cell Delivery for Cardiac Regenerative Therapy
Introduction: Microencapsulation of stem cells can prevent cell redistribution, enhance retention, and provide immunoprotection - valuable strategies that could enhance cardiac regeneration therapies. Typical microcapsules, however, are large (~300 μm), prohibiting vascular delivery and limiting enthusiasm for intramyocardial delivery due to the potential for electrical conduction abnormalities. Moreover, the lack of post-transplantation visualization limits tracking of typical microcapsule platforms. The purpose of our study was to develop small (~50 μm) microcapsules with X-Ray visibility to allow for ready, traceable delivery to the heart and thereby enhance stem cell therapy for ischemic heart disease.
Methods: Barium sulfate-impregnated alginate microcapsules (“Xcaps”) containing human mesenchymal stem cells (hMSCs) were produced using a custom microfluidic device. Xcap permeability was determined using fluorescent lectins. Size and stability after catheter administration were assessed. Xcaps were incubated at 37°C in 100% serum, 10% serum in media, and PBS for up to 60 days. In vitro viability was determined up to 22 days post-encapsulation. X-ray visibility was confirmed on a clinical angiographic system (DynaCT, Siemens Artis Zee).
Results: Xcaps were impermeable to lectins >120 kD. Xcap size and morphology were uniform after injection through a 200-μm ID microcatheter (51.9 ± 3.3 μm). Long-term incubation showed no significant change in size and morphology under the tested conditions. In vitro viability was high with indications of cell division (3.2 ± 2.1 hMSC/Xcap at day 0 vs. 5.7 ± 3.9 hMSC/Xcap with a viability of 69% at 22 days [n = 17]). Radiopacity was similar to iodinated contrast dilutions (Xcap: 2809 ± 1208 HU, 10% iohexal: 1482 ± 354 HU) with a sensitivity to as few as 100 Xcaps (5 μL).
Conclusion: Microfluidics-generated Xcaps were small, uniform and stable with selective permeability to allow free release of cytokines, but block antibodies and inflammatory cells, providing an immunoprotected environment that promotes hMSC survival and replication. The ability to deliver Xcaps through standard infusion catheters with tracking on conventional X-Ray systems appears promising for use in cardiac regenerative therapies.
- Ischemic heart disease
- Stem cell therapy
- Regenerative medicine stem cells
- Interventional cardiology
- Cardiac CT
- © 2013 by American Heart Association, Inc.