Tracking cardiac engraftment and distribution of implanted bone marrow cells: Comparing intra-aortic, intravenous, and intramyocardial delivery

Li, Shuhong; Lai, Teresa Y.Y.; Sun, Zhao; Han, Mihan; Moriyama, Eduardo H.; Wilson, Brian C.; Fazel, Shafie; Weisel, Richard D.; Yau, Terrence M.; Wu, Joseph C.; Li, Ren‐Ke

doi:10.1016/j.jtcvs.2008.11.001

Cited by 104 publications

(87 citation statements)

References 25 publications

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“…Interestingly, this study also revealed the importance of the timing of delivery with regard to the ischemic event. When cells were injected into an acute infarct there was a 50% survival rate at 2 h, but improved retention was observed when cells were injected into a more mature infarct (15). These results confirm the critical need of a cell tracking technique in the early phase after delivery of therapeutic cells, which would be possible with our ICG-labeling technique.…”

Section: Discussionsupporting

confidence: 72%

Labeling Human Embryonic Stem Cell-Derived Cardiomyocytes with Indocyanine Green for Noninvasive Tracking with Optical Imaging: An FDA-Compatible Alternative to Firefly Luciferase

et al. 2010

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Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have demonstrated the ability to improve myocardial function following transplantation into an ischemic heart; however, the functional benefits are transient possibly due to poor cell retention. A diagnostic technique that could visualize transplanted hESC-CMs could help to optimize stem cell delivery techniques. Thus, the purpose of this study was to develop a labeling technique for hESCs and hESC-CMs with the FDAapproved contrast agent indocyanine green (ICG) for optical imaging (OI). hESCs were labeled with 0.5, 1.0, 2.0, and 2.5 mg/ml of ICG for 30, 45, and 60 min at 37°C. Longitudinal OI studies were performed with both hESCs and hESC-CMs. The expression of surface proteins was assessed with immunofluorescent staining. hESCs labeled with 2 mg ICG/ml for 60 min achieved maximum fluorescence. Longitudinal studies revealed that the fluorescent signal was equivalent to controls at 120 h postlabeling. The fluorescence signal of hESCs and hESC-CMs at 1, 24, and 48 h was significantly higher compared to precontrast data (p < 0.05). Immunocytochemistry revealed retention of cell-specific surface and nuclear markers postlabeling. These data demonstrate that hESCs and hESC-CMs labeled with ICG show a significant fluorescence up to 48 h and can be visualized with OI. The labeling procedure does not impair the viability or functional integrity of the cells. The technique may be useful for assessing different delivery routes in order to improve the engraftment of transplanted hESC-CMs or other stem cell progenitors.

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Section: Discussionsupporting

confidence: 72%

Labeling Human Embryonic Stem Cell-Derived Cardiomyocytes with Indocyanine Green for Noninvasive Tracking with Optical Imaging: An FDA-Compatible Alternative to Firefly Luciferase

et al. 2010

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“…Promising results derived from preclinical and proofof-concept clinical trials using MSC for cardiac repair have shown their potential to alleviate the deleterious effects of myocardial ischemia [19,20], despite documented poor cell retention after cell injections [21,22]. To achieve widespread clinical application of cell-based therapies for post-ischemic heart failure, the selection of an optimal cell type combined with a therapeutically relevant timing, as well as a well optimized delivery method are crucial.…”

Section: Discussionmentioning

confidence: 99%

Grafts Enriched with Subamnion-Cord-Lining Mesenchymal Stem Cell Angiogenic Spheroids Induce Post-Ischemic Myocardial Revascularization and Preserve Cardiac Function in Failing Rat Hearts

Martinez

Wang

et al. 2013

Stem Cells and Development

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A crucial question in post-ischemic cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5 · 10 4 human CL-MSC coated with 2 · 10 3 human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n = 8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n = 8) and fibrin graft (FG, n = 8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n = 8) and FG-VATS (n = 7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly.

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“…In order to track engraftment and distribution of transplanted MSCs, Li and colleagues delivered male rat MSCs into female rats via intraaortic, intravenous, and intramyocardial injections, either 3 or 28 days after a myocardial infarction was induced. 43 At 24 and 48 hours after implantation, a significantly greater number of MSCs was retained in the heart when delivered through direct intramyocardial injection, rather than through other delivery routes. 43 In a swine model, Shake et al…”

Section: In Vivo Studiesmentioning

confidence: 95%

“…43 At 24 and 48 hours after implantation, a significantly greater number of MSCs was retained in the heart when delivered through direct intramyocardial injection, rather than through other delivery routes. 43 In a swine model, Shake et al…”

Section: In Vivo Studiesmentioning

confidence: 95%

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

Shahzad¹,

Li²,

Yau³

2013

The Journal of Heart and Lung Transplantation

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Objective:We investigated the roles of stem cell factor (SCF)-c-kit and stromal derived factor-1 (SDF-1)-CXCR4 signaling in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted mesenchymal stem cells (MSCs) in infarcted hearts. His constant support and sacrifices over the years have been the reason for my motivation. I will always remember his help, guidance, and the love he gave me throughout life. ! iv! ACKNOWLEDGEMENTS

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Tracking cardiac engraftment and distribution of implanted bone marrow cells: Comparing intra-aortic, intravenous, and intramyocardial delivery

Cited by 104 publications

References 25 publications

Labeling Human Embryonic Stem Cell-Derived Cardiomyocytes with Indocyanine Green for Noninvasive Tracking with Optical Imaging: An FDA-Compatible Alternative to Firefly Luciferase

Labeling Human Embryonic Stem Cell-Derived Cardiomyocytes with Indocyanine Green for Noninvasive Tracking with Optical Imaging: An FDA-Compatible Alternative to Firefly Luciferase

Grafts Enriched with Subamnion-Cord-Lining Mesenchymal Stem Cell Angiogenic Spheroids Induce Post-Ischemic Myocardial Revascularization and Preserve Cardiac Function in Failing Rat Hearts

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

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