Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-Derived Mesenchymal Stem Cells

PM R. 2018 Jun 1;S1934-1482(18)30294-6. doi: 10.1016/j.pmrj.2018.05.022. Online ahead of print.

Abstract

Background: Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections, and the effects of these agents on MSCs represents a gap in knowledge.

Objective: To investigate the biological effects of contrast media (CM) that are coinjected with MSCs.

Design: Prospective observational study.

Setting: Academic medical center.

Participants: Patient-derived clinical-grade culture expanded MSCs.

Interventions: Iohexol (Omnipaque300) was reduced to 12.5%, 25%, 50%, and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours, and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate-buffered saline as a control group.

Main outcome measures: We examined cytotoxicity of iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction of related genes were analyzed immediately after exposure (day 0) and after 2 days of exposure (day 2).

Results: Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief, 30-minute exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs.

Conclusions: CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during MSC therapy for disk-degenerative diseases.

Level of evidence: To be determined.