Abstract
In this study, murine Mesenchymal Stem Cells (MSCs) labeled with the clinically approved MRI agent Gadoteridol through a procedure based on the hypo-osmotic shock were successfully tracked in vivo in a murine model of Spinal Cord Injury (SCI). With respect to iso-osmotic incubations, the hypo-osmotic labeling significantly increased the Gd(3+) cellular uptake, and enhanced both the longitudinal relaxivity (r1) of the intracellular Gadoteridol and the Signal to Noise Ratio (SNR) measured on cell pellets, without altering the biological and functional profile of cells. A substantial T1 Contrast Enhancement after local transplantation of 3.0×10(5) labeled cells in SCI mice enabled to follow their migratory dynamics in vivo for about 10days, and treated animals recovered from the motor impairment caused by the injury, indicating unaltered therapeutic efficacy. Finally, analytical and histological data corroborated the imaging results, highlighting the opportunity to perform a precise and reliable monitoring of the cell-based therapy.
Keywords:
Cell tracking; Hypotonic swelling; Magnetic Resonance Imaging; Mesenchymal Stem Cell; Spinal Cord Injury.
Copyright © 2016 Elsevier Inc. All rights reserved.
MeSH terms
-
Analysis of Variance
-
Animals
-
Antigens, CD / metabolism
-
Calcium-Binding Proteins / metabolism
-
Cell Differentiation / physiology
-
Cell Movement
-
Cell Proliferation / physiology
-
Cell Survival
-
Cell Tracking
-
Cells, Cultured
-
Contrast Media / metabolism
-
Contrast Media / pharmacokinetics*
-
Disease Models, Animal
-
Flow Cytometry
-
Gadolinium / metabolism
-
Gadolinium / pharmacokinetics
-
Glial Fibrillary Acidic Protein / metabolism
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
Heterocyclic Compounds / metabolism
-
Heterocyclic Compounds / pharmacokinetics*
-
Hindlimb / physiopathology
-
Magnetic Resonance Imaging*
-
Mesenchymal Stem Cell Transplantation / methods
-
Mesenchymal Stem Cells / physiology*
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Microfilament Proteins / metabolism
-
Neurofilament Proteins / metabolism
-
Organometallic Compounds / metabolism
-
Organometallic Compounds / pharmacokinetics*
-
Osmosis
-
Spinal Cord Injuries / diagnostic imaging*
-
Spinal Cord Injuries / pathology*
-
Spinal Cord Injuries / surgery
-
Time Factors
Substances
-
Aif1 protein, mouse
-
Antigens, CD
-
Calcium-Binding Proteins
-
Contrast Media
-
Glial Fibrillary Acidic Protein
-
Heterocyclic Compounds
-
Microfilament Proteins
-
Neurofilament Proteins
-
Organometallic Compounds
-
gadoteridol
-
neurofilament protein H
-
Green Fluorescent Proteins
-
Gadolinium