Intra-arterial Delivery of Mesenchymal Stem Cells Following Balloon Angioplasty
Samuel Nussbaum, Mira Shoukry, Ralph Perkerson, Takahisa Kanekiyo, Houssam Farres, Albert Hakaim
Mayo Clinic Florida, Jacksonville, FL
Background: Despite therapeutic advances, peripheral arterial disease (PAD) is a rapidly progressing disease, which often results in critical limb ischemia requiring amputation. Several in vivo studies have shown that perivascular inflammation and intima dysfunction due to PAD may contribute to the development of neointimal hyperplasia. As such, there is a need for new technology to enhance conventional treatments by directly targeting the adventitia. Using a porcine model, this study aims to establish a novel mesenchymal stem cell (MSC) delivery method to treat peripheral arterial disease following balloon angioplasty.
Methods: Human bone marrow mesenchymal stem cells (BM-MSCs) were obtained from the Mayo Clinic Human Cellular Therapy Laboratory. The MSCs were fluorescently labeled with near infra-red lipophilic carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) according to the manufacturer's protocol. Freshly harvested porcine carotid arteries were obtained from Animal Biotech Industries, Inc. The vessels were prepared and allowed to hang over 15 mL tubes to keep them upright. Uninflated catheters were inserted into the vessels, and once positioned at the distal end, were inflated to occlude before injecting the vessels with either phosphate buffered saline (PBS) (3x 1mL, n=5), 100uL of DiR labeled MSCs (1x10^6cells/100uL, n=6), or 100uL of unlabeled MSCs (1x10^6cells/100uL, n=6) for five minutes. Vessels were flushed with PBS and imaged using an IVIS Spectrum In-Vivo Imaging System (PerkinElmer). GraphPad Prism was used to perform ANOVA using photons/sec. Cell viability (%) and total/viable cell counts before and after passage through the catheter device were obtained using a Vi-CELL XR Cell analyzer (Beckman Coulter) and compared in a t-test.
Results: The data from the vessel tests showed that there was a statistically significant difference in fluorescent signal detected between the vessels that were injected with DiR labelled MSCs and those that were in the control and wash through groups as the ANOVA analysis gave a p-value <.05. Figure 1 shows the total emission and max radiation of the fluorescence recorded in the vessels of each trial and the plot of this data. The cell viability test showed that viability and total cell count were not affected by passing through a balloon catheter (Figure 2).
Conclusion: The preliminary results of this study show that delivering MSCs through a balloon catheter does not harm the MSCs and is effective at getting these cells to adhere to the vessel wall following balloon angioplasty. Further ongoing studies are looking into the ability of adhered MSCs to penetrate through the angioplastied segment of arterial wall and its ability to ameliorate the neointimal hyperplasia reaction following angioplasty. 
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