A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease

Yokoyama, Shin-ichiro; Fukuda, Noboru; Li, Yuxin; Hagikura, Kazuhiro; Takayama, Tadateru; Kunimoto, Satoshi; Honye, Junko; Saito, Satoshi; Wada, Mika; Satomi, Aya; Kato, Maiko; Mugishima, Hideo; Kusumi, Yoshiaki; Mitsumata, Masako; Murohara, Toyoaki

doi:10.1016/j.yjmcc.2005.06.008

Cited by 43 publications

(44 citation statements)

References 33 publications

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“…15 MSCs have been shown to be a robust source of angiogenic factors compared with hematopoietic cells in BM. 7,27 The low-invasive local delivery of MSCs preserved cardiac function in the swine chronic MI model in our present study.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that the safety and feasibility of the cell delivery via the coronary vein in a preclinical trial with the pig models. 15 For the reasons explained below, we also selected coronary vein infusion as the route for MSC delivery into the myocardium in the present study. We did not, however, compare it with the other delivery methods (eg, intracoronary infusion and intramyocardial injection) in our hands.…”

Section: Discussionmentioning

confidence: 99%

“…Next, the guidewire was inserted into the left anterior descending coronary artery and sterilized beads were placed in the mid left anterior descending coronary artery by microcatheter (Figure 1a and b) according to a method previously described. 15 Peripheral blood was collected before and 1 and 4 days after MI. Serum creatine kinase (CK) levels were determined.…”

Section: Implant Of Stromal Cell Via Coronary Vein T Sato Et Almentioning

confidence: 99%

“…As hopeful alternatives, new methods of cell transplantation have recently been reported. [15][16][17][18] We previously demonstrated the safety and efficacy of retrograde injection of BMNCs via the coronary vein into the myocardium through a single balloon infusion catheter in a swine MI model. 15 Our group conducted this study for two purposes: first, to investigate whether the low invasive delivery of MSCs via the coronary vein restores cardiac function in chronic ischemic cardiomyopathy model; second, to explore the mechanism behind the improvement, if any improvement is found.…”

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confidence: 99%

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Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization

Sato

Iso

Uyama

et al. 2011

Laboratory Investigation

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Few reports have examined the effects of adult bone marrow multipotent stromal cells (MSCs) on large animals, and no useful method has been established for MSC implantation. In this study, we investigate the effects of MSC infusion from the coronary vein in a swine model of chronic myocardial infarction (MI). MI was induced in domestic swine by placing beads in the left coronary artery. Bone marrow cells were aspirated and then cultured to isolate the MSCs. At 4 weeks after MI, MSCs labeled with dye (n ¼ 8) or vehicle (n ¼ 5) were infused retrogradely from the anterior interventricular vein without any complications. Left ventriculography (LVG) was performed just before and at 4 weeks after cell infusion. The ejection fraction (EF) assessed by LVG significantly decreased from baseline up to a follow-up at 4 weeks in the control group (Po0.05), whereas the cardiac function was preserved in the MSC group. The difference in the EF between baseline and follow-up was significantly greater in the MSC group than in the control group (Po0.05). The MSC administration significantly promoted neovascularization in the border areas compared with the controls (Po0.0005), though it had no affect on cardiac fibrosis. A few MSCs expressed von Willebrand factor in a differentiation assay, but none of them expressed troponin T. In quantitative gene expression analysis, basic fibroblast growth factor and vascular endothelial growth factor (VEGF) levels were significantly higher in the MSC-treated hearts than in the controls (Po0.05, respectively). Immunohistochemical staining revealed VEGF production in the engrafted MSCs. In vitro experiment demonstrated that MSCs significantly stimulated endothelial capillary network formation compared with the VEGF protein (Po0.0001). MSC infusion via the coronary vein prevented the progression of cardiac dysfunction in chronic MI. This favorable effect appeared to derive not from cell differentiation, but from enhanced neovascularization by angiogenic factors secreted from the MSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Implant Of Stromal Cell Via Coronary Vein T Sato Et Almentioning

confidence: 99%

mentioning

confidence: 99%

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Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization

Sato

Iso

Uyama

et al. 2011

Laboratory Investigation

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“…Recently, Yokoyama et al showed that retrograde delivery of BMCs via the coronary vein induced angiogenesis and improved the function of the infarcted heart. 27 Retrograde infusion might be an alternative strategy in the clinical setting. Further evaluation and direct comparison of delivery routes is required in a large-animal model.…”

Section: Study Limitationsmentioning

confidence: 99%

Delivery Route in Bone Marrow Cell Transplantation Should be Optimized According to the Etiology of Heart Disease

Nakajima

Sakakibara

Tambara

et al. 2008

Circ J

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Preparation of BMCsBMCs were harvested from 8-week-old syngenic and transgenic male C57Bl/6 mice expressing enhanced green fluorescent protein (GFP), by flushing the femurs and tibias Circ J 2008; 72: 1528 -1535 (Received August 23, 2006 revised manuscript received April 28, 2008; accepted May 9, 2008 Background Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. Methods and Results MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM-and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV-and IMgroups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. Conclusions In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation. (Circ J 2008; 72: 1528 -1535

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Catheter‐based retrograde coronary sinus infusion is a practical delivery technique for introducing biological molecules into the cardiac system

Rodenberg

Patel

Shirley

et al. 2019

Cathet Cardio Intervent

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Objectives To demonstrate coronary sinus (CS) retrograde catheterization as a practicable technique for delivering biologics into the heart. Background There are many options to deliver biologics into the heart. However, there is no single optimal technique when considering safety, biologic retention, and reproducibility. Retrograde delivery has the potential to address many of these concerns. This study evaluated retrograde CS infusion of luciferase‐expressing plasmid in a porcine model using the Advance® CS Coronary Sinus Infusion Catheter and bioluminescence imaging to track the expression of the infused biological markers. Methods Plasmid was delivered retrograde into the CS in one of three infusion volumes. Twenty‐four hours post‐infusion, hearts were excised and underwent bioluminescence imaging to characterize the expression of the infusates. Heart and lung biopsies were also assessed for luciferase expression using RT‐qPCR. Results Retrograde infusion was safe and successful in all nine test subjects. Luciferase detection was inconsistent in the low volume group. Bioluminescence was confined predominantly along the posterolateral left ventricle for medium volume infusions and was more broadly dispersed along the anterior side of the heart for high volume infusions. Tissue mRNA analysis corroborated the bioluminescence results, with the highest concentration of luciferase expression localized in the left ventricle. Conclusions Retrograde CS infusion is a promising technique for delivering biological molecules to the heart. Specifically, this study demonstrated that the low pressure coronary venous system accommodates a wide range of infusion volumes and that biological infusates can be maintained in situ following the resumption of coronary venous flow.

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A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease

Cited by 43 publications

References 33 publications

Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization

Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization

Delivery Route in Bone Marrow Cell Transplantation Should be Optimized According to the Etiology of Heart Disease

Catheter‐based retrograde coronary sinus infusion is a practical delivery technique for introducing biological molecules into the cardiac system

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