Iron Particles for Noninvasive Monitoring of Bone Marrow Stromal Cell Engraftment into, and Isolation of Viable Engrafted Donor Cells from, the Heart

Stuckey, Daniel J.; Carr, Carolyn A.; Martin‐Rendon, Enca; Tyler, Damian J.; Willmott, Corinne; Cassidy, P J; Hale, Sarah; Schneider, Jürgen; Tatton, Louise; Harding, Siân E.; Radda, George K.; Watt, Suzanne M.; Clarke, Kiernan

doi:10.1634/stemcells.2006-0074

Cited by 122 publications

(133 citation statements)

References 40 publications

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“…We, and others, have shown that the contrast generated by ironlabeled cells increases with the amount of iron/voxel but that this is only linear at low iron loadings; the change in contrast reaches a saturation plateau at higher iron loadings. 6,7 When quantifying the presence of iron-labeled stem cells over time, most studies measure the "signal void volume" 8,9 or the "number of black pixels", 10,11 and present the change relative to the first imaging time point.…”

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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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: 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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“…5 Over the past 10 years, many preclinical studies and clinical trials have used SPIO and cardiac magnetic resonance (CMR) imaging to deliver, track, or determine the efficacy of stem cell therapy in the heart. [6][7][8][9][10][11][12][13][14] The detected signal is used to estimate the number of cells. Even recently, SPIO was still used to label and assess the long-term (2 months) survival of human-induced pluripotent stem cellderived cardiomyocytes in infarcted myocardia of mini-pigs.…”

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confidence: 99%

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

Huang

Yang

et al. 2015

IJN

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Purpose The long-lasting hypointensities in cardiac magnetic resonance (CMR) were believed to originate from superparamagnetic iron oxide (SPIO)-engulfed macrophages during long-term stem cell tracking. However, the iron clearance capacity of the ischemic heart was limited. Therefore, we speculated that the extracellular SPIO particles may also be involved in the generation of false-positive signals. Methods and results Male swine mesenchymal stem cells (MSCs) were incubated with SPIO for 24 hours, and SPIO labeling had no significant effects on either cell viability or differentiation. In vitro studies showed that magnetic resonance failed to distinguish SPIO from living SPIO-MSCs or dead SPIO-MSCs. Two hours after the establishment of the female swine acute myocardial infarction model, 2×10 7 male SPIO-labeled MSCs (n=5) or unlabeled MSCs (n=5) were transextracardially injected into the infarcted myocardium at ten distinct sites. In vivo CMR with T2 star weighted imaging-flash-2D sequence revealed a signal void corresponding to the initial SPIO-MSC injection sites. At 6 months after transplantation, CMR identified 32 (64%) of the 50 injection sites, where massive Prussian blue-positive iron deposits were detected by pathological examination. However, iron particles were predominantly distributed in the extracellular space, and a minority was distributed within CD 68 -positive macrophages and other CD 68 -negative cells. No sex-determining region Y DNA of donor MSCs was detected. Conclusion CMR hypointensive signal is primarily caused by extracellular iron particles in the long-term tracking of transplanted MSCs after myocardial infarction. Consideration should be given to both the false-positive signal and the potential cardiac toxicity of long-standing iron deposits in the heart.

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“…Adequate methods for monitoring these aspects have recently been described; it was shown recently that iron-oxide labelled cells can be visualized by MRI thereby allowing migration and engraftment to be directly monitored in the heart. 65 In addition, hybrid imaging systems (two or more imaging modalities) are emerging, [66][67][68][69] paving the way for simultaneously monitoring the heart at a global, regional and molecular level under the conditions of interest. Based on these trends, the future of imaging seems to be in multi-scale approaches; from global to regional to imaging at the molecular level, in a multimodality based manner.…”

Section: The Use Of Imaging Technologiesmentioning

confidence: 99%

Cardiovascular Research: Past, Present and Future

Fiedler¹

2015

Heart Res Open J

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Cardiovascular disease remains a leading cause of death and significant burden on healthcare systems worldwide. While interventional and preventative medicine has considerably changed the face of clinical practice, at the molecular level, treatment has not altered in recent decades and is still directed towards alleviating symptoms or mitigating the underlying cause rather than regenerating damaged heart muscle. This is surprising, given the explosion of research in this area in the 1970's, and the fact that research output has continued to increase exponentially. With the incidence of heart failure on the rise, a trend predicted to continue, it is imperative that treatment strategies are improved. The development and adoption of molecular interventions might therefore present the most fruitful avenue in providing the greatest impact on mortality rates. This commentary aims to reflect on the earliest documented studies of human cardiovascular physiology, to surgical interventions in the 12 th , to the first molecular studies in the 20 th , to current pharmacological treatments. With this knowledge in mind, the future of molecular approaches in treating heart failure and cardiovascular conditions will be considered.

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Iron Particles for Noninvasive Monitoring of Bone Marrow Stromal Cell Engraftment into, and Isolation of Viable Engrafted Donor Cells from, the Heart

Cited by 122 publications

References 40 publications

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

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

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

Cardiovascular Research: Past, Present and Future

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