Hossein Nejadnik MD, PhD, Presenter: Nothing to Disclose

Deju Ye PhD, Abstract Co-Author: Nothing to Disclose

olga lenkov BSC, Abstract Co-Author: Nothing to Disclose

Jessica Donig BA, Abstract Co-Author: Nothing to Disclose

Jianghong Rao PhD, Abstract Co-Author: Nothing to Disclose

Heike E. Daldrup-Link MD, Abstract Co-Author: Nothing to Disclose

Limited survival of transplanted stem cells represents a significant bottleneck for successful cartilage regeneration outcomes. The goal of this study was to develop a non-invasive MR imaging test for detection of stem cell apoptosis, using a caspase-3-activatable small molecular Gd-chelate (C-SNAM).

The C-SNAM probe underwent extensive nanocharacterization by relaxivity measurements, high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Viable and apoptotic (Mitomycin C treated) rat adipose derived stem cells (rASCs) were incubated with C-SNAM or a non-activatable control Gd-chelate and underwent in vitro MR imaging. Then, five athymic rats, with implanted viable or apoptotic Fluc-transduced rASCs in osteochondral defects, underwent MR and optical imaging before and after intra-articular injection of C-SNAM. T1-relaxation times of different groups were compared with a Student’s t-test, using a p < 0.05.

The r1 relaxivity of the C-SNAM probe increased from 10.2 ± 1.5 mM-1s-1 to 19.0 ± 0.5 mM-1s-1, after activation by caspase-3 (p < 0.05). HPLC analysis showed a fast cyclization of the probe (half-life t1/2 < 1h) to form cyclized products. The formation of GdNPs after caspase-3 activation confirmed by DLS and TEM. In vitro, apoptotic rASCs demonstrated significant, ~50% shortening of T1-relaxation times after incubation with C-SNAM compared to viable rASCs, while T1-times after exposure with the control probe were not significantly different. In vivo, apoptotic MASI showed significantly lower T1-relaxation times compared with viable MASI at 30 minutes after C-SNAM intra-articular injection. Bioluminescent imaging confirmed cellular apoptosis of C-SNAM enhancing rASC implants.

We present a novel approach for non-invasive, high-resolution in vivo detection of stem cell apoptosis with a novel caspase-sensitive contrast agent for MR imaging. This new imaging biomarker could be applied to a wide variety of stem cell therapies, facilitate optimizations of MASI strategies, and ultimately improve successful tissue regeneration outcomes.

The described novel MR contrast agent, a strong candidate for clinical translation, could improve MR evaluations of stem cell transplants and direct patients with failed MASI to repeated interventions.

Nejadnik, H, Ye, D, lenkov, o, Donig, J, Rao, J, Daldrup-Link, H, Diagnosis of Stem Cell Apoptosis in Arthritic Joints with MRI.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14015138.html