Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson’s disease

Abstract

Background:We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats. Methods: hMSCs were labeled both with a membrane intercalating dye, emitting in the near-infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of nearinfrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology. Results: In vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging. Conclusion: Near-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients.

Intranasal Treatment of Central Nervous System Dysfunction in Humans

“…Another research group used a similar rodent model of Parkinson’s disease but a different intranasal delivery method and different method (near-infrared live imaging) for detecting cells in the brain (89). Additionally, they utilized human, as opposed to rat stem cells, in contrast to (88).…”

Imaging Gliomas with Nanoparticle-Labeled Stem Cells

“…Among this type of imaging technique, near infrared (NIR) imaging achieves a higher penetration depth of up to several centimeters and provides more specific signals by capturing light of a NIR wavelength. [ 109 110 ] Thus, this technique holds broad application potential in the in vivo imaging of physiological, metabolic, and molecular functions. NIR imaging requires NIR probes to emit a light signal under excitation.…”

Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

“…Fluorescent microscopy, [H3]-thymidine, and near-infrared live imaging have previously been utilized to track MSCs following IND; florescent microscopy has also been used to image NSCs following IND [2,16,44,112,113]. …”