Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction

Wisenberg, Gerald; Lekx, Katie S.; Zabel, Pam; Kong, Huafu; Mann, Rupinder; Zeman, Peter; Datta, Sudip Kumar; Culshaw, C.; Merrifield, Peter A.; Bureau, Y; Wells, G.; Sykes, Jane; Prato, Frank S.

doi:10.1186/1532-429x-11-11

Cited by 31 publications

(24 citation statements)

References 67 publications

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“…Given this and some ethical considerations as to potential adverse effects of GFP-modified cells, its use was considered inappropriate for cell tracking in client-owned dogs. Instead, we used PKH26 red fluorescent dye, a lipophilic cell membrane stain that has previously been used for tracking of a variety of different cell types (Wisenberg et al, 2009). Data in the present study showed that cell viability and population doubling time of MSCs in culture was not significantly affected by PKH26 staining, corroborating findings of a previously reported study in which no effect on cell growth or proliferation was observed (Shao-Fang et al, 2011).…”

Section: Discussionsupporting

confidence: 93%

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs

Linon

Spreng

Rytz

et al. 2014

The Veterinary Journal

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Current research indicates that exogenous stem cells may accelerate reparative processes in joint disease but, no previous studies have evaluated whether bone marrow cells (BMCs) target the injured cranial cruciate ligament (CCL) in dogs. The objective of this study was to investigate engraftment of BMCs following intra-articular injection in dogs with spontaneous CCL injury. Autologous PKH26-labelled BMCs were injected into the stifle joint of eight client-owned dogs with CCL rupture. The effects of PKH26 staining on cell viability and PKH26 fluorescence intensity were analysed in vitro using a MTT assay and flow cytometry. Labelled BMCs in injured CCL tissue were identified using fluorescence microscopy of biopsies harvested 3 and 13 days after intra-articular BMC injection. The intensity of PKH26 fluorescence declines with cell division but was still detectable after 16 days. Labelling with PKH26 had no detectable effect on cell viability or proliferation. Only rare PKH26-positive cells were present in biopsies of the injured CCL in 3/7 dogs and in synovial fluid in 1/7 dogs. No differences in transforming growth factor-β1, and interleukin-6 before and after BMC treatment were found and no clinical complications were noted during a 1 year follow-up period. In conclusion, BMCs were shown to engraft to the injured CCL in dogs when injected into the articular cavity. Intra-articular application of PKH26-labelled cultured mesenchymal stem cells is likely to result in higher numbers of engrafted cells that can be tracked using this method in a clinical setting.

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Section: Discussionsupporting

confidence: 93%

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs

Linon

Spreng

Rytz

et al. 2014

The Veterinary Journal

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“…As in other cardiac MRE studies [4,12,13], we did not exclude the blood pool from our analysis. The rationale behind this is that wall vibration is transmitted into a confined fluid by pressure or nonevanescent waves (see e.g.…”

Section: Methodsmentioning

confidence: 99%

Elasticity-based determination of isovolumetric phases in the human heart

Elgeti

Beling

Hamm

et al. 2010

Journal of Cardiovascular Magnetic Resonance

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Background/MotivationTo directly determine isovolumetric cardiac time intervals by magnetic resonance elastography (MRE) using the magnitude of the complex signal for deducing morphological information combined with the phase of the complex signal for tension-relaxation measurements.MethodsThirty-five healthy volunteers and 11 patients with relaxation abnormalities were subjected to transthoracic wave stimulation using vibrations of approximately 25 Hz. A k-space-segmented, ECG-gated gradient-recalled echo steady-state sequence with a 500-Hz bipolar motion-encoding gradient was used for acquiring a series of 360 complex images of a short-axis view of the heart at a frame rate of less than 5.2 ms. Magnitude images were employed for measuring the cross-sectional area of the left ventricle, while phase images were used for analyzing the amplitudes of the externally induced waves. The delay between the decrease in amplitude and onset of ventricular contraction was determined in all subjects and assigned to the time of isovolumetric tension. Conversely, the delay between the increase in wave amplitude and ventricular dilatation was used for measuring the time of isovolumetric elasticity relaxation.ResultsWave amplitudes decreased during systole and increased during diastole. The variation in wave amplitude occurred ahead of morphological changes. In healthy volunteers the time of isovolumetric elasticity relaxation was 75 ± 31 ms, which is significantly shorter than the time of isovolumetric tension of 136 ± 36 ms (P < 0.01). In patients with relaxation abnormalities (mild diastolic dysfunction, n = 11) isovolumetric elasticity relaxation was significantly prolonged, with 133 ± 57 ms (P < 0.01), whereas isovolumetric tension time was in the range of healthy controls (161 ± 45 ms; P = 0.053).ConclusionThe complex MRE signal conveys complementary information on cardiac morphology and elasticity, which can be combined for directly measuring isovolumetric tension and elasticity relaxation in the human heart.

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“…Assessing MO on EGE requires a fixed, high inversion-time (TI) and is generally performed at ~2-4 min following contrast administration (Figure 6). With the recent advent of accelerated high-resolution perfusion sequences (1.5 mm × 1.5 mm spatial resolution, 8 slices acquired over 2 R-R intervals) [21], it is now possible to detect true first pass MO and quantify it for the entire LV (Figure 6). …”

Section: Reviewmentioning

confidence: 99%

CMR of microvascular obstruction and hemorrhage in myocardial infarction

2012

Journal of Cardiovascular Magnetic Resonance

143

144

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Microvascular obstruction (MO) or no-reflow phenomenon is an established complication of coronary reperfusion therapy for acute myocardial infarction. It is increasingly recognized as a poor prognostic indicator and marker of subsequent adverse LV remodeling. Although MO can be assessed using various imaging modalities including electrocardiography, myocardial contrast echocardiography, nuclear scintigraphy, and coronary angiography, evaluation by cardiovascular magnetic resonance (CMR) is particularly useful in enhancing its detection, diagnosis, and quantification, as well as following its subsequent effects on infarct evolution and healing. MO assessment has become a routine component of the CMR evaluation of acute myocardial infarction and will increasingly play a role in clinical trials of adjunctive reperfusion agents and strategies. This review will summarize the pathophysiology of MO, current CMR approaches to diagnosis, clinical implications, and future directions needed for improving our understanding of this common clinical problem.

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Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction

Cited by 31 publications

References 67 publications

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs

Elasticity-based determination of isovolumetric phases in the human heart

CMR of microvascular obstruction and hemorrhage in myocardial infarction

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