In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging

Flögel, Ulrich; Ding, Zhaoping; Hardung, Hendrik; Jander, Sebastian; Reichmann, Gaby; Jacoby, Christoph; Schubert, Rolf; Schrader, Jürgen

doi:10.1161/circulationaha.107.737890

Cited by 318 publications

(460 citation statements)

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“…Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences. [16][17][18][19][37][38][39][40] Using the 3D bSSFP sequence, we injected and detected 1.5×10 6 Cell Sense-labeled hMSC in vivo on day 0 using a spatial resolution of 2 mm 3 (2 µL). If we assume that on day 0 all of the injected cells are present and evenly distributed, then we detected 30,000 cells per voxel.…”

Section: Cell Detection With Bssfpmentioning

confidence: 99%

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In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

Ribot¹,

Gaudet²,

Chen³

et al. 2014

IJN

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Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron.

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Section: Cell Detection With Bssfpmentioning

confidence: 99%

“…Examples of 19 F MR imaging performed to date include: monitoring inflammation (tumor models, rheumatoid arthritis, lung injuries, and after ischemia in the lung or brain), [16][17][18][19] detection of T cell and dendritic cell migration, 20,21 and tracking the fate of transplanted hematopoietic and neural stem cells.…”

Section: Introductionmentioning

confidence: 99%

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

Ribot¹,

Gaudet²,

Chen³

et al. 2014

IJN

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“…[84][85][86] Additionally, in vivo perfluorocarbon emulsion infusion followed by 19 F MRI has been shown to preferentially detect areas of inflammation both in the CNS and systemically via preferential uptake by CD68+ macrophages, providing a non-invasive measure of disease activity in murine models of inflammatory disease. [87][88][89][90] Thus, the advantage of these labelling modalities includes the ability to directly visualise (and potentially in an EAE mouse model in which human MSCs engineered to express a myelin oligodendrocyte glycoprotein-specific receptor were intranasally delivered and found to significantly improve EAE symptoms better than non-engineered human MSCs, and prevented further EAE induction. 93 Indeed, while MSCs are a promising therapeutic resource, other stem cell sources may supplant MSCs in the future.…”

Section: Dmd = Disease-modifying Drug; Ipsc = Induced Pluripotent Stementioning

confidence: 99%

Cell-Based Therapeutic Strategies in Multiple Sclerosis

Rossman

Cohen²

2014

European Neurological Review

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Multiple sclerosis (MS) is an immune-mediated disease in which acute inflammatory demyelination leads to axonal injury and neurodegeneration, and is manifested clinically by relapsing-remitting neurological deficits superimposed on chronic accumulation of disability. MS treatments are largely immunomodulatory with little, if any, effect on neurodegeneration. Mesenchymal stem cells (MSCs) are pluripotent cells derived from adult tissues with intrinsic anti-inflammatory and repair-promoting properties. They cross the blood-brain barrier and target perivascular spaces, which are the sites of inflammatory cell infiltration in MS. In vitro, MSCs can be purified and expanded, labelled for post-transplant tracking and be manipulated to express surface receptors or neurotrophic factors for central nervous system (CNS) targeting or neuroprotection, respectively. Animal models of MS, traumatic CNS injury and neurodegenerative diseases demonstrate clinical and pathological benefits following MSC transplantation. Potentially, MSCs can be used to treat MS patients at various disease stages, which is the current focus of ongoing phase I/II clinical trials at multiple centres. KeywordsMultiple sclerosis, mesenchymal stem cell, clinical trial, induced pluripotent stem cell, experimental autoimmune encephalitis exposure and smoking, and these likely interact heterogeneously with genetic factors across the MS population. 5,6 Thus, the natural history of MS varies between patients. The average age of onset is typically in the third decade and there is a peak prevalence in the fifth decade of life. Paediatric MS is rarer, particularly in patients aged younger than 9 years of age, though there is a growing recognition of early-onset MS and its implications for earlier disability than adult-onset MS. 4,7,8 The prevalence of MS has been estimated at one to two per 1,000 in North America and northern Europe, but the incidence and prevalence vary geographically, seem to increase with latitude and appear to be increasing, particularly in women.9 A systematic review of the financial burden of MS in the US found a range of $8,528-54,244 per patient per year, with approximately 77 % representing direct costs to the patient (i.e. prescription medications), making MS the second most costly disease in the US behind congestive heart failure. Current Treatments in Relapsing-Remitting Multiple SclerosisThe mainstay of MS therapy has been anti-inflammatory diseasemodifying drugs (DMDs) that target various immune system pathways to decrease or prevent the continuation of an immune-mediated destructive process. 4 In the clinical context, the goal of therapy is twofold: 1) minimising accumulated disability associated with clinical relapses; and 2) preventing the MRI lesion activity, which can occur in the absence of clinical symptoms. The mechanisms of action, route of delivery, safety, tolerability and side-effect profiles differ between DMDs, though they all serve these two principles. Thus, DMD treatment should be considered early follow...

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“…The results of the study of phagocytes detection in vivo using perfluorcarbonic emulsion by the method of magnetic resonance in experimental ischemic damage of myocardium and brain have been published [18]. The model of acute ischemia of a myocardium and brain in mice with subsequent intravenous injection of perfluor carbonic emulsion has been employed in the study.…”

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confidence: 99%