MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

Namestnikova, Daria; Gubskiy, Ilya; Габашвили, А. Н.; Sukhinich, K. K.; Melnikov, Pavel; Vishnevskiy, Daniil A.; Соловьева, А. А.; Vitushev, E; Chekhonin, V. P.; Gubsky, Leonid V.; Yarygin, K. N.

doi:10.1088/1742-6596/886/1/012012

Cited by 7 publications

(10 citation statements)

References 8 publications

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“…MRI also showed that the highest engraftment correlated with reduced cerebral blood flow and led to increased mortality 26 . The propensity of MSCs to induce microocclusions was also observed in several other studies where MRI cell-tracking was instrumental in developing safe transplantation protocols 6, 13, 22, 32, 33 . Similarly to MSCs, biodistribution of neural stem cells (C17.2) injected IA in a mouse model of hypoxia/ischemia was visualized on MRI scans shortly after injection 3 .…”

Section: Imaging After Completed Cell Injectionsupporting

confidence: 55%

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Intra-Arterial Delivery of Cell Therapies for Stroke

Guzman

Janowski

Walczak

2018

Stroke

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Section: Imaging After Completed Cell Injectionsupporting

confidence: 55%

“…After the infusion rate was reduced to 0.2ml/min, no injury was observed 6 . Microinfarcts were observed in another study with an injection velocity at 0.3ml/min 22 . Similar lesions were also observed with the injection of PBS at a rate of 0.16ml/min 13 .…”

Section: Safety Of Ia Injection After Strokementioning

confidence: 89%

Intra-Arterial Delivery of Cell Therapies for Stroke

Guzman

Janowski

Walczak

2018

Stroke

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“…Intra-arterial injection of cells via the internal carotid artery is an effective route of MSCs delivery to brain in preclinical studies of the effects of cell therapy in experimental brain disorders [ 51 , 52 ]. Due to optimization of the injection parameters completed in our preliminary experiments [ 32 ], we did not observe cerebral embolic events after cell administration. The vast majority of transplanted hMSCs was carried away from brain with blood flow, while a small fraction penetrated the brain tissue and soon after injection could be visualized using MRI.…”

Section: Discussionmentioning

confidence: 99%

“…After cell transplantation the catheter was removed, the stump was electrocoagulated, and incision was closed with a 3–0 silk suture. The described cell infusion parameters (cell dose not more that 5x10 5 in 1 ml, infusion velocity 100 μl/1 min with maintenance of blood flow in ICA and ligation of PPA) were selected during a preliminary study [ 32 ] and proved to prevent serious adverse events such as cerebral embolism.…”

Section: Methodsmentioning

confidence: 99%

Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain

et al. 2017

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In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

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“…The dose of transplanted cells was the highest dose warranting safe IA administration without cerebral embolism. The dose of 5 × 10 5 pMSC (average cell diameter 24–25 μm) was established in our previous study ( Namestnikova et al, 2017a ). The 7 × 10 5 dose for drNPC was slightly higher, since drNPC have smaller diameter (average cell diameter 13–15 μm).…”

Section: Methodsmentioning

confidence: 99%

Intra-Arterial Stem Cell Transplantation in Experimental Stroke in Rats: Real-Time MR Visualization of Transplanted Cells Starting With Their First Pass Through the Brain With Regard to the Therapeutic Action

et al. 2021

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Cell therapy is an emerging approach to stroke treatment with a potential to limit brain damage and enhance its restoration after the acute phase of the disease. In this study we tested directly reprogrammed neural precursor cells (drNPC) derived from adult human bone marrow cells in the rat middle cerebral artery occlusion (MCAO) model of acute ischemic stroke using human placenta mesenchymal stem cells (pMSC) as a positive control with previously confirmed efficacy. Cells were infused into the ipsilateral (right) internal carotid artery of male Wistar rats 24 h after MCAO. The main goal of this work was to evaluate real-time distribution and subsequent homing of transplanted cells in the brain. This was achieved by performing intra-arterial infusion directly inside the MRI scanner and allowed transplanted cells tracing starting from their first pass through the brain vessels. Immediately after transplantation, cells were observed in the periphery of the infarct zone and in the brain stem, 15 min later small numbers of cells could be discovered deep in the infarct core and in the contralateral hemisphere, where drNPC were seen earlier and in greater numbers than pMSC. Transplanted cells in both groups could no longer be detected in the rat brain 48–72 h after infusion. Histological and histochemical analysis demonstrated that both the drNPC and pMSC were localized inside blood vessels in close contact with the vascular wall. No passage of labeled cells through the blood brain barrier was observed. Additionally, the therapeutic effects of drNPC and pMSC were compared. Both drNPC and pMSC induced substantial attenuation of neurological deficits evaluated at the 7th and 14th day after transplantation using the modified neurological severity score (mNSS). Some of the effects of drNPC and pMSC, such as the influence on the infarct volume and the survival rate of animals, differed. The results suggest a paracrine mechanism of the positive therapeutic effects of IA drNPC and pMSC infusion, potentially enhanced by the cell-cell interactions. Our data also indicate that the long-term homing of transplanted cells in the brain is not necessary for the brain’s functional recovery.

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MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

Cited by 7 publications

References 8 publications

Intra-Arterial Delivery of Cell Therapies for Stroke

Intra-Arterial Delivery of Cell Therapies for Stroke

Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain

Intra-Arterial Stem Cell Transplantation in Experimental Stroke in Rats: Real-Time MR Visualization of Transplanted Cells Starting With Their First Pass Through the Brain With Regard to the Therapeutic Action

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