Effects of MRI Contrast Agents on the Stem Cell Phenotype

Abstract

The ultimate therapy for ischemic stroke is restoration of blood supply in the ischemic region and regeneration of lost neural cells. This might be achieved by transplanting cells that differentiate into vascular or neuronal cell types, or secrete trophic factors that enhance self-renewal, recruitment, long-term survival, and functional integration of endogenous stem/progenitor cells. Experimental stroke models have been developed to determine potential beneficial effect of stem/progenitor cell-based therapies. To follow the fate of grafted cells in vivo, a number of noninvasive imaging approaches have been developed. Magnetic resonance imaging (MRI) is a high-resolution, clinically relevant method allowing in vivo monitoring of cells labeled with contrast agents. In this study, labeling efficiency of three different stem cell populations [mouse embryonic stem cells (mESC), rat multipotent adult progenitor cells (rMAPC), and mouse mesenchymal stem cells (mMSC)] with three different (ultra)small superparamagnetic iron oxide [(U)SPIO] particles (Resovist, Endorem, Sinerem) was compared. Labeling efficiency with Resovist and Endorem differed significantly between the different stem cells. Labeling with (U)SPIOs in the range that allows detection of cells by in vivo MRI did not affect differentiation of stem cells when labeled with concentrations of particles needed for MRI-based visualization. Finally, we demonstrated that labeled rMAPC could be detected in vivo and that labeling did not interfere with their migration. We conclude that successful use of (U)SPIOs for MRI-based visualization will require assessment of the optimal (U)SPIO for each individual (stem) cell population to ensure the most sensitive detection without associated toxicity.

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

“…Obviously, the low efficiency of loading the SPIO particles into cells and the cytotoxicity of previously formulated particles limit their usage as an image probe (21). It has been demonstrated by several groups that SPIO particles have little toxicity and few side effects on cell proliferation and activity (21,22). However, certain study results have indicated the inhibitory effect of SPIO particles on MSC differentiation and its signaling mechanism (23).…”

“…Some investigators have already demonstrated the feasibility of in vivo tracking of transplanted MSCs by labeling them with magnetic SPIO particles (18)(19)(20). Obviously, the low efficiency of loading the SPIO particles into cells and the cytotoxicity of previously formulated particles limit their usage as an image probe (21). It has been demonstrated by several groups that SPIO particles have little toxicity and few side effects on cell proliferation and activity (21,22).…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…Due to the partially complicated labeling protocols, simplified strategies using clinically approved materials (e. g. Endorem ® /Feridex ® , Superfect ® , Lipofectamine Plus ® , poly-Llysine (PLL), protamine) and low cell toxicity have been described in recent years [148,149]. While most studies do not describe any significant changes in cell behavior (e. g. apoptosis rate, proliferation index, differentiation behavior) [150,151], individual studies show changes in migration behavior and the ability to form colonies [152], in cell vitality [153], in differentiation behavior [154], or in the expression pattern [152]. By the same token, the influence of cell labeling on the long-term behavior of cells and the course of disease is currently unclear [155] and must be studied more closely in the future [156].…”

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

“…61 In brief, MSC labeled with NPs were plated into six-well plates at 2,000 cells per well with complete growth medium and medium was changed every 2 days. The living cell population was assessed by automatic cell counting with the CASY Model TT, every 2 days from Day 2 to Day 10.…”