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
journal contributionposted on 09.01.2020, 14:33 by Shashank Shankar Chetty, Selvarasu Praneetha, Arumugam Vadivel Murugan, Kavitha Govarthanan, Rama Shanker Verma
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.
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B 16F C 57BL micecell-assisted anticancer therapyflow-cytometry techniquesCIS-ZMGS-NCs-labeled WJ-MSCsmultifunctional nanocrystalsTumor Mice Model Mesenchymalgene expressions2 hdetection sensitivityr 1r 2CuInSGdNIRtumor resultstransfection agentsHUMnnoninvasive multimodality imagingcancer theranosticsCD 44SMCAimaging modalitiesvivo imagingWhartondeep-tissue diagnosismultilineage differentiationmMplasma mass-spectroscopy analysesMultimodality Imagingelectroporation processMSCs engraftmentsubcutaneous melanomamagnetofluorescent CIS-ZMGS-NCs-labeled WJ-MSCsconfocal microscopytumor-homing abilitiesZnSFDA approvaltumor environmentnoninvasive imaging technologynext-generation nanobioprobeCIS-ZMGS-NCs-labeled WJ-MSCs exhibit near-infraredCD 1056 hCD 90MSCs-specific markers