Cell tracking of chromium‐labeled mesenchymal stem cells using laser ablation inductively coupled plasma imaging mass spectrometry

Abstract

Rationale Mesenchymal stem cells (MSCs) are widely used in regenerative medicine research. Evaluating the biodistribution of MSCs is important for determining whether the cells have reached the target tissue, and the time that the stem cells reside in each area is required to estimate the duration of efficacy. Methods A laser ablation inductively coupled plasma imaging mass spectrometry (LAICP‐IMS) method was developed for highly sensitive and quantitative surface analysis of metal elements for solid samples. We evaluated the usefulness of a cell‐tracking system with LAICP‐IMS to investigate the biodistribution of mouse mesenchymal stem cells (mMSCs) labeled with the natural composition of chromium (Cr) in mice. To prepare the dosing solution, mMSCs were incubated with both Na2CrO4 and fluorescent labeling solutions. The concentration of the cells was adjusted by vehicle solution at 2.0 to 2.5 × 107 cells/mL, and the dosing suspension of mMSCs was administered by intramuscular or intravenous injection to the mice. Results Thigh muscle sections after intramuscular injection of chromium‐ and fluorescence‐labeled mMSCs were analyzed by LAICP‐IMS and fluorescence microscopy, respectively. 52Cr mass spectrometry and fluorescence signals were detected in the same thigh muscle sections after administration of mMSCs. A half‐body section was also analyzed by LAICP‐IMS. 52Cr signals were mainly detected in the lungs. Conclusions The 52Cr signals were observed in sections through the thigh muscle and half body after intramuscular and intravenous administration, respectively, of Cr‐labeled mMSCs to mice. Our results suggest that LAICP‐IMS is a sensitive and useful technique to evaluate biodistribution in cell therapy research.

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

“…This could suggest that MSCs do not distribute to other organs after intramuscular injection. This was in line with the findings of similar studies performed following intramuscular injection [62][63][64], with MSCs remaining at the injection site, but without MSCs distributing to organs. However, it has been demonstrated that, despite the lack of distribution of MSCs, when injected intramuscularly in a contralateral muscle to an inflamed area, MSCs are capable of reducing inflammation.…”

Quantitative Comparison of Gold Nanoparticle Delivery via the Enhanced Permeation and Retention (EPR) Effect and Mesenchymal Stem Cell (MSC)-Based Targeting

“…20–30 μm) is approximately five times larger than the narrow pulmonary capillaries ( ca . 5 μm of diameter), when MSCs circulate through the lungs following injections, they most likely will come into contact with surface vasculature, leading to an eventual MSC arrest in the capillaries, followed partially by subsequent extravasation through the vascular wall into the lung tissue. ,− However, not all Au NPs delivered by the MSCs to the lungs finally penetrated the lung tissue: For the MSC-mediated Au NP delivery, there was a temporal decline in lung accumulation, followed by a temporal increase in liver accumulation, thereby suggesting the translocation of Au NPs initially entrapped within the lungs to the liver. In addition, it must be stressed that MSCs will die over time in the body following intravenous injection, which additionally may have led to the redistribution of Au NPs in the organs as observed.…”