Abstract
Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.
Highlights
Magnetic resonance imaging (MRI) provides several advantages over radionuclide imaging for monitoring stem cell therapies
We evaluated the feasibility of detecting in real-time, cell delivery, cell migration and cell death of transplanted stem cells, using an MRI dual-contrast technique, and validated the findings with bioluminescence imaging (BLI)
In order to detect the presence of human mesenchymal stem cells by MRI, cells were dual magnetically labelled in the absence of a transfection agent, using commercially available contrast agents
Summary
Magnetic resonance imaging (MRI) provides several advantages over radionuclide imaging for monitoring stem cell therapies. The small-sized, fast-diffusing, gadolinium chelates would diffuse away from the slow-diffusing SPIONs and generate a diffused T1 contrast enhancement in the vicinity of the dead cells (Fig. 1) This dynamic T1 contrast enhancement in the vicinity of the transplanted cells would serve as a local imaging marker for cell death. Based on our previous studies, we determined that it is possible to separate both T2/T2* and T1 signals using appropriate acquisition parameters, when both agents are as little as ~15 μ m away from each other[38,39] The feasibility of this technique to detect, cell delivery, cell migration and cell death was evaluated in vitro using MRI phantoms and in vivo using an image-guided, radiation-induced murine model of brain injury, in both immune-competent and immune-deficient mice
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