A novel X-ray-visible microencapsuled mesenchymal stem cell therapy for peripheral arterial disease

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)