| Autor: |
Anna IM; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Sathy BN; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Ashokan A; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Gowd GS; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Ramachandran R; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Kochugovindan Unni AK; Central Lab Animal Facility, Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Kochi, Kerala 682041, India., Manohar M; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Chulliyath D; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Nair S; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India., Bhakoo K; Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), Helios, Singapore 138667, Singapore., Koyakutty M; Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India. |
| Abstrakt: |
In vivo tracking of transplanted stem cells to monitor their migration, biodistribution, and engraftment in the host tissue is important for assessing the efficacy of stem cell therapeutics. Here, we report a biomineral nanocontrast agent, iron doped calcium phosphate nanoparticles (nCP:Fe), for the in vivo tracking of stem cells in brain using magnetic resonance imaging (MRI). We have synthesized ∼100 nm sized nCP nanoparticles doped with 9.81 wt % Fe 3+ . In vitro studies using mesenchymal stem cells (MSCs) showed excellent biocompatibility for nCP:Fe with ∼87% labeling efficiency under optimized conditions (100 μg/mL, 6 h). Most importantly, the labeling was not found to affect the neurogenic differentiation potential of MSCs. MRI of labeled cells (∼22.34 pg Fe/cell) showed significant reduction in T2 relaxation time from 195 to 89 ms, rendering dark contrast. In vivo transplantation of labeled cells (1 × 10 6 cells) in external capsule of healthy rat brain showed a clearly distinguishable hypointense (dark) region in T2 weighted MR images, which remained visible up to 30 days. Subsequently, MRI tracking of labeled MSCs transplanted intracerebrally, 3 mm near to the LPS induced inflammatory site in brain, showed successful migration of labeled MSCs toward the site of inflammation. The cell migration was confirmed ex vivo by Prussian-blue (Fe 3+ ) and Alizarin-red (Ca 2+ ) staining of tissue sections, where individual cells were found migrated to the site of inflammation over a period of 30 days. In summary, our results clearly show that, as a biocompatible mineral composition, nCP:Fe is a promising magnetic nanocontrast agent for MRI based cell tracking in vivo. |
