Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy

Memon, Imran A.; Sawa, Yoshiki; Miyagawa, Shigeru; Taketani, Satoshi; Matsuda, Hikaru

doi:10.1016/j.jtcvs.2005.02.024

Cited by 68 publications

(29 citation statements)

References 27 publications

(27 reference statements)

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“…In line with the results of a previous study which showed that combined intramyocardial delivery of SkM and BM cells gave superior prognosis as compared with either of the two [36], our approach indirectly harnesses the beneficial effects of SkM and BM cells, the two potential candidate cell types for heart cell therapy, together with cytokine therapy. Moreover, we demonstrate that the combination of therapeutic gene transfer with cell therapy may represent a promising new avenue of investigation in the treatment of patients with ischemic LV dysfunction.…”

Section: Discussionsupporting

confidence: 83%

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

Elmadbouh

Haider

Jiang

et al. 2007

Journal of Molecular and Cellular Cardiology

165

110

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We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1α) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1α gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1α gene into syngenic SkM were achieved using FuGene™6/phSDF-1α (3:2v/w, 4h transfection) with 125μM ZnCl 2 (p<0.001). After characterization for transgene overexpression by immunostaining, ELISA, and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n=12/group) to receive 70μl DMEM without cells (group-1) or containing 1.5×10 6 non-transfected (group-2) or SDF-1α transfected SkM (group-3). On day-4 post-transplantation (in 4 animals/group), marked expression of SDF-1α/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31 + , C-kit + and CD34 + cells was highest in group-3 hearts (p<0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p<0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p<0.05) as compared with groups-1 and -2. We conclude that ex-vivo SDF-1α transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.

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Section: Discussionsupporting

confidence: 83%

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

Elmadbouh

Haider

Jiang

et al. 2007

Journal of Molecular and Cellular Cardiology

165

110

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“…Several studies The infusion of EPCs or isolated hematopoietic progenitor cells promotes neovascularization of ischemic have shown that the prosurvival phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway may play an important role myocardium and improves the ventricular function after myocardial ischemia in both human and animal study in endothelial cells and EPCs (20,114). Thus, statins, VEGF, EPO, estrogen, and shear stress have also been (40, 62,69). In a canine model, circulating endothelial progenitor cells could be a substitute source of endothealso reported to modulate the PI3K/Akt pathway (20,27,41,51,86,100).…”

Section: In Cardiovascular Diseasesmentioning

confidence: 99%

Transplantation of Endothelial Progenitor Cells as Therapeutics for Cardiovascular Diseases

et al. 2009

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With better understanding of endothelial progenitor cells (EPCs), many therapeutic approaches to cardiovascular diseases have been developed. This article will review novel research of EPCs in promoting angiogenesis, vasculogenesis, and endothelialization, as a design for future clinical treatment. Cell therapy has the potential to supply stem/progenitor cells and multiple angiogenic factors to the region of ischemia. The efficacy of EPC transplantation may be impaired by low survival rate, insufficient cell number, and impaired function in aging and diseases. Combination of EPCs or cells primed with growth factors or genetic modification may improve the therapeutic efficacy. The molecular mechanism involved in EPC repairing processes is essential. Thus, we have also addressed the molecular mechanism of mobilization, homing, and differentiation of EPCs. The potential of therapeutic neovascularization, angiogenic factor therapy, and cell transplantation have been elucidated. Based on past experience and actual knowledge, future strategies for EPC therapy will be proposed in order to fully exploit the potential of EPC transplantation with clinical relevance for cardiovascular disease applications.

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“…Miyagawa et al implanted both BMMCs and skeletal myoblasts into patients with severe heart failure caused by chronic ischemic heart disease under a left ventricular assist device (LVAD), and observed improvements in the global systolic and diastolic function in a series of LVAD-off tests [65]. This clinical therapy in which these two cell types were transplanted together into the ischemic myocardium probably enhanced the secretion of growth factors such as hepatocyte growth factor, rather than inducing angiogenesis and myogenesis [66]. Table 4.…”

Section: Other Clinical Studies In Cellular Cardiomyoplastymentioning

confidence: 99%

“…Some unique approaches using both myoblasts and BMCs to regenerate distressed myocardium have been reported. Memon et al demonstrated that the implantation of both myoblasts and BMCs enhanced the secretion of growth factors and improved cardiac performance compared with each singlecell therapy [66].…”

Section: Paracrine Effect Of Cytokines After Cellular Cardiomyoplastymentioning

confidence: 99%

From bench to bedside, work in cell-based myocardial regeneration therapy

Miyagawa

Sawa²

2014

JBiSE

Self Cite

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In clinical cellular cardiomyoplasty, bone marrow cells and myoblasts are introduced mainly to ischemic cardiomyopathy tissue via several cell delivery systems, such as needle injection or catheter. These clinical studies have demonstrated the safety and feasibility of this technique, but its effectiveness for treating heart failure, especially in the long term, is still under discussion. Neither of these cell types can differentiate into cardiomyocytes; rather, they improve the failing heart mainly by the paracrine effects of some cytokines, such as Hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF). Thus, many researchers have a great interest in stem cells, which exist in bone marrow, circulating blood, atrium, and adipose tissue, and can differentiate into cardiomyocytes. Although several stem cells with the potential to differentiate into various cell types have been reported, few can differentiate into cardiomyocytes. Moreover, beating cells that can demonstrate synchronized contraction with native cardiomyocytes are critical for the complete repair of severe heart failure. Therefore, stem cells with a high differentiation capacity should be explored for the goal of completely repairing severely damaged myocardium. In this review, we summarize the clinical protocols and basic experiments for cellular cardiomyoplasty using bone marrow cells, myoblasts, and other stem cells.

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Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy

Abstract: Combined autologous cellular therapy induced both myogenesis and angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.

Cited by 68 publications

References 27 publications

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

Transplantation of Endothelial Progenitor Cells as Therapeutics for Cardiovascular Diseases

From bench to bedside, work in cell-based myocardial regeneration therapy

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