Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells Labeled with Mn2+ and Gd3+ Co-Doped CuInS2–ZnS Nanocrystals for Multimodality Imaging in a Tumor Mice Model
| Autor: | Shashank Shankar Chetty, Rama Shanker Verma, Arumugam Vadivel Murugan, Kavitha Govarthanan, S. Praneetha |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
biology Mesenchymal stem cell CD44 02 engineering and technology 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Umbilical cord 0104 chemical sciences law.invention medicine.anatomical_structure Confocal microscopy law Wharton's jelly Cancer research biology.protein medicine General Materials Science CD90 Stem cell 0210 nano-technology Ex vivo |
| Zdroj: | ACS Applied Materials & Interfaces. 12:3415-3429 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.9b19054 |
| Popis: | Mesenchymal stem cell (MSCs) therapy has recently received profound interest as a targeting platform in cancer theranostics because of inherent tumor-homing abilities. However, the terminal tracking of MSCs engraftment by fluorescent in situ hybridization, immuno-histochemistry, and flow-cytometry techniques to translate into clinics is still challenging because of a dearth of inherent MSCs-specific markers and FDA approval for genetic modifications of MSCs. To address this challenge, a cost-effective noninvasive imaging technology based on multifunctional nanocrystals (NCs) with enhanced detection sensitivity, spatial-temporal resolution, and deep-tissue diagnosis is needed to be developed to track the transplanted stem cells. A hassle-free labeling of human umbilical cord Wharton's Jelly (WJ)-derived MSCs with Mn2+ and Gd3+ co-doped CuInS2-ZnS (CIS-ZMGS) NCs has been demonstrated in 2 h without requiring an electroporation process or transfection agents. It has been found that WJ-MSCs labeling did not affect their multilineage differentiation (adipocyte, osteocyte, chondrocyte), immuno-phenotypes (CD44+, CD105+, CD90+), protein (β-actin, vimentin, CD73, α-SMCA), and gene expressions. Interestingly, CIS-ZMGS-NCs-labeled WJ-MSCs exhibit near-infrared (NIR) fluorescence with a quantum yield of 84%, radiant intensity of ∼3.999 × 1011 (p/s/cm2/sr)/(μW/cm2), magnetic relaxivity (longitudinal r1 = 2.26 mM-1 s-1, transverse r2 = 16.47 mM-1 s-1), and X-ray attenuation (78 HU) potential for early noninvasive multimodality imaging of a subcutaneous melanoma in B16F10-tumor-bearing C57BL/6 mice in 6 h. The ex vivo imaging and inductively coupled plasma mass-spectroscopy analyses of excised organs along with confocal microscopy and immunofluorescence of tumor results also significantly confirmed the positive tropism of CIS-ZMGS-NCs-labeled WJ-MSCs in the tumor environment. Hence, we propose the magnetofluorescent CIS-ZMGS-NCs-labeled WJ-MSCs as a next-generation nanobioprobe of three commonly used imaging modalities for stem cell-assisted anticancer therapy and tracking tissue/organ regenerations. |
| Databáze: | OpenAIRE |
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