Expression of clMagR/clCry4 protein in mBMSCs provides T2-contrast enhancement of MRI
Source abstract
Abstract
Here, we propose for the first time the evaluation of magnetosensitive clMagR/clCry4 as a magnetic resonance imaging (MRI) reporter gene that imparts sensitivity to endogenous contrast in eukaryotic organisms. Using a lentiviral vector, we introduced clMagR/clCry4 into C57BL/6 mice-derived bone marrow mesenchymal stem cells (mBMSCs), which could specifically bind with iron, significantly affected MRI transverse relaxation, and generated readily detectable contrast without adverse effects in vivo. Specifically, clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which cells recruit exogenous iron and convert these stores into an MRI-detectable contrast; this is not achievable with control cells. Additionally, Prussian blue staining was performed together with ultrathin cell slices to provide direct evidence of natural iron-bearing granules being detectable on MRI. Hence, it was inferred that the sensitivity of MRI detection should be correlated with clMagR/clCry4 and exogenous iron. Taken together, the clMagR/clCry4 has great potential as an MRI reporter gene. STATEMENT OF SIGNIFICANCE: In this study, we propose the evaluation of magnetosensitive clMagR/clCry4 as an MRI reporter gene, imparting detection sensitivity to eukaryotic mBMSCs for endogenous contrast. At this point, the clMagR and clCry4 were located within the cytoplasm and possibly influence each other. The clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which protein could specifically bind with iron and convert these stores into MRI-detectable contrast; this is not achieved by control cells. The viewpoint was speculated that the clMagR/clCry4 and exogenous iron were complementary to each other. Additionally, Prussian blue staining was performed together with TEM observations to provide direct evidence that the iron-bearing granules were sensitive to MRI.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Cancer Research and Treatments · Photoreceptor and optogenetics research · Electromagnetic Fields and Biological Effects
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (65)
Show source-provided references
1. Molecular imaging in drug discovery and development10.1038/nrd1007 ↗
2. Nanomaterials for theranostics: recent advances and future challenges10.1021/cr300213b ↗
3. Towards clinically translatable in vivo nanodiagnostics10.1038/natrevmats.2017.14 ↗
4. Multimodality imaging probes: design and challenges10.1021/cr9003538 ↗
5. Second thoughts about CT imaging10.1126/science.331.6020.1002 ↗
6. Molecular imaging in drug development10.1038/nrd2290 ↗
7. Challenges for molecular magnetic resonance imaging10.1021/cr100025t ↗
8. MRI detection of transcriptional regulation of gene expression in transgenic mice10.1038/nm1497 ↗
9. Technology insight: in vivo cell tracking by use of MRI10.1038/ncpcardio0659 ↗
10. Iron oxide nanoparticle based contrast agents for magnetic resonance imaging10.1021/acs.molpharmaceut.6b00839 ↗
11. Molecular imaging in cancer10.1126/science.1125949 ↗
12. Chemistry of MRI contrast agents: current challenges and new frontiers10.1021/acs.chemrev.8b00363 ↗
13. Recent developments in magnetic diagnostic systems10.1021/cr500698d ↗
14. Iron oxide based nanoparticles for multimodal imaging and magnetoresponsive therapy10.1021/acs.chemrev.5b00112 ↗
15. Noninvasive cell-tracking methods10.1038/nrclinonc.2011.141 ↗
16. MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter10.1038/nbt.3714 ↗
17. Ferritin: a versatile building block for bionanotechnology10.1021/cr400011b ↗
18. Magnetic resonance reporter gene imaging10.7150/thno.3634 ↗
19. Clinical imaging in regenerative medicine10.1038/nbt.2993 ↗
20. A magnetic protein biocompass10.1038/nmat4484 ↗
21. Searching for unity in diversity of animal magnetoreception: from biology to quantum mechanics and back
22. A rationally designed building block of the putative magnetoreceptor MagR10.1002/bem.22413 ↗
23. Modulation of MagR magnetic properties via iron-sulfur cluster binding10.1038/s41598-021-03344-2 ↗
24. Characterization of iron binding in IscA, an ancient iron-sulphur cluster assembly protein10.1042/bj20031702 ↗
25. Structural conversions of synthetic and protein-bound iron-sulfur clusters10.1021/acs.chemrev.6b00276 ↗
26. The oxygen sensitivity of spinach ferredoxin and other iron-sulfur proteins formation of protein-bound sulfur-zero10.1016/S0021-9258(18)62463-9 ↗
27. Iron-sulfur clusters as biosensors of oxidants and iron10.1016/S0968-0004(96)10024-4 ↗
28. Subsite-differentiated analogs of native iron sulfide [4Fe-4S]2+ clusters: preparation of clusters with five- and six-coordinate subsites and modulation of redox potentials and charge distributions10.1021/ja00163a028 ↗
29. Magnetic noise enabled biocompass10.1103/PhysRevLett.124.128101 ↗
30. Orbital interactions, electron delocalization and spin coupling in iron-sulfur clusters10.1016/0010-8545(95)07011-L ↗
31. Iron-sulfur clusters as biological sensors: the chemistry of reactions with molecular oxygen and nitric oxide10.1021/ar5002507 ↗
32. Crystal structure of the ancient, Fe-S scaffold IscA reveals a novel protein fold10.1021/bi035440s ↗
33. Magnetic sensitivity of cryptochrome 4 from a migratory songbird10.1038/s41586-021-03618-9 ↗
34. Long-distance navigation and magnetoreception in migratory animals10.1038/s41586-018-0176-1 ↗
35. Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon10.1073/pnas.1907875116 ↗
36. The radical-pair mechanism of magnetoreception
37. Revealing the molecular identity of the photoactivation reaction10.1021/ja3074819 ↗
38. Solvent driving force ensures fast formation of a persistent and well-separated radical pair in plant cryptochrome10.1021/ja510550g ↗
39. Electron spin relaxation in cryptochrome-based magnetoreception10.1039/C5CP06731F ↗
40. Electron spin relaxation can enhance the performance of a cryptochrome-based magnetic compass sensor10.1088/1367-2630/18/6/063007 ↗
41. Spin relaxation of radicals in cryptochrome and its role in avian magnetoreception10.1063/1.4958624 ↗
42. Transfection of clMagR/clCry4 imparts MR-T2 imaging contrast properties to living organisms (E. coli) in the presence of Fe3+ by endogenous formation of iron oxide nanoparticles10.3389/fmolb.2023.1119356 ↗
43. Mesenchymal stem cells in health and disease10.1038/nri2395 ↗
44. Mesenchymal stem cell-based therapy10.1021/mp3005148 ↗
45. Directing stem cell fate: the synthetic natural product connection10.1021/acs.chemrev.7b00015 ↗
46. Next-generation stem cells - ushering in a new era of cell-based therapies10.1038/s41573-020-0064-x ↗
47. Retroviral DNA integration10.1021/acs.chemrev.6b00125 ↗
48. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector10.1126/science.272.5259.263 ↗
49. Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors10.1073/pnas.0404180101 ↗
50. Clinical use of lentiviral vectors10.1038/s41375-018-0106-0 ↗
51. Translational control of retroviruses10.1038/nrmicro1599 ↗
52. Ferric ammonium citrate - what's in it?10.1002/ejic.201500782 ↗
53. Real-time detection of hydroxyl radical generated at operating electrodes via redox-active adduct formation using scanning electrochemical microscopy10.1021/jacs.2c06278 ↗
54. pH Effect on the H2O2-induced deactivation of Fe-N-C catalysts10.1021/acscatal.0c00948 ↗
55. Reactive Oxygen Species (ROS)-based nanomedicine10.1021/acs.chemrev.8b00626 ↗
56. Overexpression of the MRI reporter genes ferritin and transferrin receptor affect iron homeostasis and produce limited contrast in mesenchymal stem cells10.3390/ijms160715481 ↗
57. Reporter gene approaches for mapping cell fate decisions by MRI: promises and pitfalls10.1002/cmmi.1590 ↗
58. NMR reveals pathway for ferric mineral precursors to the central cavity of ferritin10.1073/pnas.0908082106 ↗
59. Ferritins: dynamic management of biological iron and oxygen chemistry10.1021/ar0302336 ↗
60. Moving Fe2+ from ferritin ion channels to catalytic OH centers depends on conserved protein cage carboxylates10.1073/pnas.1318417111 ↗
61. Ferritin: a promising nanoreactor and nanocarrier for bionanotechnology10.1021/acsbiomedchemau.2c00003 ↗
62. Solving biology's iron chemistry problem with ferritin protein nanocages10.1021/ar500469e ↗
63. Iron loading induces cholesterol synthesis and sensitizes endothelial cells to TNF alpha-mediated apoptosis10.1016/j.jbc.2021.101156 ↗
64. Astrocytic expression of ZIP14 (SLC39A14) is part of the inflammatory reaction in chronic neurodegeneration with iron overload10.1002/glia.23806 ↗
65. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells10.1038/74464 ↗