Abstract P039: Encapsulation of Human Mesenchymal Stem Cells in Alginate Microspheres to Enhance Paracrine-Mediated Vascular Recovery
Bone marrow cells migrate to ischemic areas and facilitate revascularization mostly through paracrine mechanisms. As a result, therapeutic strategies for vascular repair have focused on increasing the concentration of these cells at the site of ischemia by direct injection. These strategies have led to encouraging results in clinical trials, yet the number of cells that remain at the site of delivery is very low.
The goal of this study is to design an effective cell delivery system to enhance revascularization by maintaining large numbers of cells at the ischemic site, thus increasing the local delivery of angiogenic factors. To achieve this goal, we encapsulated bone marrow derived human mesenchymal stem cells (hMSCs) in non-degradable, barium-gelled alginate spheres prior to delivery to the ischemic site. Our microspheres are biocompatible, do not generate a fibrotic response, and are stable for extended periods of time. They prevent incorporation of cells into the neighboring tissue and protect implanted cells from immune mediated clearance or wash out by the host capillary and lymphatic systems. The microspheres allow diffusion of molecules as large as 80 kDa (which includes most angiogenic factors) but not of larger molecules such as IgG. To test this cell delivery system in vivo, we used a model of murine hind limb ischemia in athymic nude mice. We delivered encapsulated hMSCs, or, as a control, empty capsules, to the ischemic muscle. At various time points, we retrieved the capsules by gentle scooping, then assessed the viability of the encapsulated cells and their protein secretion profile. Approximately 70% of the cells remained viable within the first week and 10-20% within the first month after implantation. In addition, encapsulated cells secreted angiogenic factors (VEGF, bFGF, HGF, angiogenin) in vitro and in vivo. We also assessed recovery of perfusion in the hind limb and found that delivery of encapsulated cells enhanced vascular recovery as compared to empty capsules.
The results obtained from this study show that microcapsules are an effective delivery vehicle of therapeutic cells for vascular repair. Encapsulation represents a powerful and highly translatable tool to enhance cell-based therapies in cardiovascular disease.
- © 2011 by American Heart Association, Inc.