PT  - JOURNAL ARTICLE
AU  - Kedziorek, Dorota
AU  - Gilson, Wesley
AU  - Fu, Yingli
AU  - Barnett, Bradley
AU  - Huang, Gary
AU  - Bulte, Jeff
AU  - Hofmann, Lawrence
AU  - Kraitchman, Dara
TI  - A novel X-ray-visible microencapsuled mesenchymal stem cell therapy for peripheral arterial disease
DP  - 2010 May 01
TA  - Journal of Nuclear Medicine
PG  - 45--45
VI  - 51
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/51/supplement_2/45.short
4100  - http://jnm.snmjournals.org/content/51/supplement_2/45.full
SO  - J Nucl Med2010 May 01; 51
AB  - 45 Objectives Cell microencapsulation was developed to overcome transplant rejection and poor engraftment rates in many cell therapies. However, cell transplant tracking still remains problematic. In this study, a novel X-ray-visible microencapsulated mesenchymal stem cells (MSCs) therapy was explored for cell tracking and efficacy for therapeutic arteriogenesis in a peripheral arterial disease (PAD) in rabbits. Methods Allogeneic rabbit MSCs were encapsulated by modifying the alginate poly-L-lysine alginate method (1) with the incorporation of 10% barium sulfate to create X-ray visible capsules (XMSCs). Subsequently XMSCs or empty barium microcapsules (XCaps) were injected into the rabbit PAD model (n=10). Immediately after (baseline) and 2 weeks post transplantation X-ray angiography (Infinix CC-I, Toshiba) was performed to investigate capsule visibility/ persistence using normalized signal-to-noise (SNR) ratios and collateral vessel development with modified TIMI frame counts, i.e., difference in time of filling of the popliteal bifurcation between the non-ischemic and ischemic limb. CD31 immunohistochemistry was used to estimate vascular density. Results XMSCs and XCaps injection sites were visible and appeared similar on fluoroscopic images at baseline (SNR: 14.0±2.5 vs. 10.1±4.3, P=NS). No difference was also seen between baseline and two week visibility (SNR: 12.1±3.9 vs. 13.1±2.7, P=NS). An enhanced therapeutic effect with XMSCs was shown compared to XCaps (TIMI: 4.2±0.8 vs. 12.2±5 s, P<0.002). Higher TIMI values, i.e., increased delay to filling in the ischemic limb, were correlated with low vessel density around microcapsules (R2=0.42). Conclusions In a rabbit model, we have demonstrated the ability to track MSCs over several weeks using clinical X-ray systems and enhance therapeutic angiogenesis relative to sham injections. Research Support 1. F. Lim, A. M. Sun, Science 210, 908 (Nov 21, 1980)