Imaging Neural Stem Cell Graft-Induced Structural Repair in Stroke

Abstract

Stem cell therapy ameliorates motor deficits in experimental stroke model. Multimodal molecular imaging enables real-time longitudinal monitoring of infarct location, size, and transplant survival. In the present study, we used magnetic resonance imaging (MRI) and positron emission tomography (PET) to track the infarct evolution, tissue repair, and the fate of grafted cells. We genetically engineered embryonic stem cell-derived neural stem cells (NSCs) with a triple fusion reporter gene to express monomeric red fluorescence protein and herpes simplex virus-truncated thymidine kinase for multimodal molecular imaging and SPIO labeled for MRI. The infarct size as well as fate and function of grafted cells were tracked in real time for 3 months using MRI and PET. We report that grafted NSCs reduced the infarct size in animals with less than 0.1 cm3 initial infarct in a dose-dependent manner, while larger stroke was not amenable to such beneficial effects. PET imaging revealed increased metabolic activity in grafted animals and visualized functioning grafted cells in vivo. Immunohistopathological analysis demonstrated that, after a 3-month survival period, grafted NSCs dispersed in the stroke-lesioned parenchyma and differentiated into neurons, astrocytes, and oligodendrocytes. Longitudinal multimodal imaging provides insights into time course dose-dependent interactions between NSC grafts and structural changes in infarcted tissue.

In vivomagnetic resonance imaging of iron oxide-labeled, intravenous-injected mesenchymal stem cells in kidneys of rabbits with acute ischemic kidney injury: detection and monitoring at 1.5 T

“…20 In our study, we choose the Resovist, a clinically approved SPIO particle used in our study, has been demonstrated as a nanoparticle with high uptake and long persistence in human MSC throughout a period of several weeks, 21 our MSCs can be well labeled with 25 mg/mL SPIO particles without affecting the viability and labeling efficiency.…”

Tracking Stem Cells for Cellular Therapy in Stroke

“…Prior to transplantation, hNSCs were genetically modified to express a triple fusion (TF) reporter gene encoding monomeric red fluorescent protein (mRFP), firefly luciferase (Luc), and a truncated version of HSV1-tk (HSV-ttk). hNSCs also were labeled with SPIO particles prior to transplantation, thus allowing us to simultaneously track cells by BLI, PET, and MRI and also to measure the functional efficacy of hNSCs on stroke recovery [74]. Using this multimodal imaging strategy, we found that grafted hNSCs reduced the infarct size of moderate strokes in a dose-dependent manner, while larger strokes could not be spared in this manner.…”

Taurine Protected Against the Impairments of Neural Stem Cell Differentiated Neurons Induced by Oxygen–Glucose Deprivation

“…NSCs can be isolated from the adult striatal tissue [1,2]. They are considered as candidate for cell replacement therapy in various neurological diseases, particularly in ischemic stroke-induced cerebral damages [3][4][5][6][7]. Ischemic stroke accounts for 80 % of all strokes [8].…”