Implantation of bone marrow stromal cells labeled with superparamagnetic nanoparticles into injured brain and imaging their fate by magnetic resonance

Our study demonstrates that MSCs only migrate into an injured brain region. The commercially available contrast agent Endorem can be used as a cell marker for noninvasive MR tracking of implanted stem cells

The Relationship Between Changes in Intrinsic Optical Signals and Cell

Changes in intrinsic optical signals could be related to cell swelling; however, the evidence is not compelling. We measured light transmittance, ECS volume fraction (#), and extracellular K in rat spinal cord slices during electrical stimulation and the application of elevated potassium, NMDA, or anisoosmotic solutions. Dorsal root stimulation (10 Hz/1 min) induced an elevation in extracellular K to 6 -- 8 mM, a light transmittance increase of 6 -- 8%, and a relative ECS volume decrease of less than 5%; all of these changes had different time courses. The application of 6 or 10 mM K or NMDA (10 M) had no measurable effect on #, but light transmittance increased by 20--25%. The application of 50 or 80 mM K evoked a 72% decrease in # while the light transmittance increase remained as large as that in6or10mMK . While the change in # persisted throughout the 45-min application, light transmittance, after peaking in 6 -- 8 min, quickly returned to control levels and decreased below them. Astrocytic hypertrophy was observed in 6, 10, and 50 mM K . The same results followed the application of 10 M NMDA or hypotonic solution (160 mmol/kg). The elevation of extracellular K after NMDA application, corresponding to increased neuronal activity, had a similar time course as the light transmittance changes. Furosemide, Cl -free, or Ca -free solution blocked or slowed down the decreases in #, while the light transmittance increases were unaffected. In hypertonic solution (400 mmol/kg), # increased by 30 -- 40%, while light transmittance decreased by 15--20%. Thus, light transmittance changes do not correlate with changes in ECS volume but are associated with neuronal activity and morphological changes in astrocytes

Metabolic changes in focal brain ischemia in rats treated with human induced pluripotent stem cell-derived neural precursors confirm the beneficial effect of transplanted cells

There is currently no treatment for restoring lost neurological function after stroke. A growing number of studies have highlighted the potential of stem cells. However, the mechanisms underlying their beneficial effect have yet to be explored in sufficient detail. In this study, we transplanted human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) in rat temporary middle cerebral artery occlusion (MCAO) model. Using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) we monitored the effect of cells and assessed lesion volume and metabolite changes in the brain. We monitored concentration changes of myo-inositol (Ins), Taurine (Tau), Glycerophosphocholine+Phosphocholine (GPC+PCh), N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA+NAAG), Creatine+Phosphocreatine (Cr+PCr), and Glutamate+Glutamine (Glu+Gln) in the brains of control and iPSC-NP-transplanted rats. Based on initial lesion size, animals were divided into small lesion and big lesion groups. In the small lesion control group (SCL), lesion size after 4 months was three times smaller than initial measurements. In the small lesion iPSC-NP-treated group, lesion volume decreased after 1 month and then increased after 4 months. Although animals with small lesions significantly improved their motor skills after iPSC-NP transplantation, animals with big lesions showed no improvement. However, our MRI data demonstrate that in the big lesion iPSC-NP-treated (BTL) group, lesion size increased only up until 1 month after MCAO induction and then decreased. In contrast, in the big lesion control group, lesion size increased throughout the whole experiment. Significantly higher concentrations of Ins, Tau, GPC+PCh, NAA+NAAG, Cr+PCr, and Glu+Gln were found in in contralateral hemisphere in BTL animals 4 months after cell injection. Lesion volume decreased at this time point. Spectroscopic results of metabolite concentrations in lesion correlated with volumetric measurements of lesion, with the highest negative correlation observed for NAA+NAAG. Altogether, our results suggest that iPSC-NP transplantation decreases lesion volume and regulates metabolite concentrations within the normal range expected in healthy tissue. Further research into the ability of iPSC-NPs to differentiate into tissue-specific neurons and its effect on the long-term restoration of lesioned tissue is necessary