Tao Wu1, Hai Nie2, Allan B Dietz3, David R Salek4, Jay Smith5, Andre J van Wijnen6, Wenchun Qu7. 1. Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN. 2. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. 4. Division of Pain Medicine, Mayo Clinic, Rochester, MN. 5. Departments of Physical Medicine and Rehabilitation, Radiology, and Anatomy, Mayo Clinic, Rochester, MN. 6. Departments of Orthopedic Surgery, Biochemistry and Molecular Biology, and Physiology and Biomedical Engineering, Mayo Clinic, 200 First St SW, Rochester, MN 55902. Electronic address: vanWijnen.Andre@mayo.edu. 7. Department of Physical Medicine and Rehabilitation and Division of Pain Medicine, Spine Center, Mayo Clinic, 200 First St SW, Rochester, MN 55902. Electronic address: qu.wenchun@mayo.edu.
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.
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.
Authors: Amel Dudakovic; Emily T Camilleri; Eric A Lewallen; Meghan E McGee-Lawrence; Scott M Riester; Sanjeev Kakar; Martin Montecino; Gary S Stein; Hyun-Mo Ryoo; Allan B Dietz; Jennifer J Westendorf; Andre J van Wijnen Journal: J Cell Physiol Date: 2015-01 Impact factor: 6.384
Authors: Hai Nie; Eva Kubrova; Tao Wu; Janet M Denbeigh; Christine Hunt; Allan B Dietz; Jay Smith; Wenchun Qu; Andre J van Wijnen Journal: PM R Date: 2019-05-30 Impact factor: 2.298