Abstract 18310: Therapeutic Use of Encapsulated Genetically Engineered Mesenchymal Stem Cells for Vascular Regeneration
Background: We have previously shown that encapsulation of mesenchymal stem cells (MSCs) in alginate improves cell retention and efficacy of stem cell therapies in the hind limb model of vascular insufficiency. Erythropoietin (EPO), a hematopoietic cytokine, is also known as an angiogenic factor. The purpose of this study is to evaluate the efficacy of encapsulated, gene transfected MSCs as therapeutic strategy for enhancing collateral formation in hind limb ischemia model by using EPO transfected MSCs (MSC-EPO).
Methods and Results: MSCs and MSCs-EPO were encapsulated into alginate microcapsules. Hind limb ischemia was induced by ligating and excising both the super facial femoral artery and vein in the left leg. The mice were implanted with either empty capsules, encapsulated 1 X 106MSCs (MSC group), encapsulated 0.9 X 106 MSCs + 0.1 X 106MSCs-EPO (low EPO group), or encapsulated 0.5 X 106of MSC + 0.5 X 106of MSCs-EPO (high EPO group). Blood analysis was performed on post-operative day (POD) 14 and 28 and histological evaluation with immunohistochemistry was performed on POD 14 (n=4/group). To evaluate the functional recovery, a spontaneous running wheel test was performed between POD 14 to POD 21. On POD 14, there was no significant change in hematocrit in 4 groups. On POD 28, the hematocrit in the high EPO group was significantly increased (57.2±4.6%) Histological evaluation revealed that the density of collateral vessels was increased in both the low and high EPO groups. (0.7±0.04, 0.84±005, 0.98±0.05 and 1.06±0.06 respectively) Although the high EPO group had a much higher density of collateral vessels, the running distance was significantly reduced to two third of the other groups.(6507±208.3, 6223±294.0, 6067±510.5 and 3952±322.1m/day, respectively)
Conclusion: The use of alginate encapsulation of MSCs is a viable strategy for site directed gene therapy. Our data show that EPO can be effectively delivered resulting in an improvement in collateral vessel formation. However, chronic over-expression of EPO may cause adverse effects likley as a result of increased blood viscosity.
- © 2013 by American Heart Association, Inc.