Transplantation of angiogenin-overexpressing mesenchymal stem cells synergistically augments cardiac function in a porcine model of chronic ischemia

Huang, Shengdong; Lu, Fanglin; Xu, Xunyu; Liu, Xiaohong; Zhao, Xianxian; Zhao, Bao-zhen; Wang, Li; Gong, Daozhi; Yuan, Yuan; Zhao, Xu

doi:10.1016/j.jtcvs.2006.08.021

Cited by 33 publications

(18 citation statements)

References 23 publications

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“…ANG is an angiogenic protein with amino acid sequence resembling bovine pancreatic ribonuclease A [35], which binds to actin on the surface of endothelial cells [36] and becomes endocytosed, and then translocated to the nucleus to promote blood vessel formation [37]. Like the VEGF-A, transplantation of MSCs that overexpress ANG resulted in improvement of myocardial perfusion and cardiac function through increased vasculogenesis [8,38]. However, while the overexpression of the VEGF-A and/or ANG successfully increases the angiogenic paracrine activity of MSCs, the risks associated with use of genetically modified cells are considered to be significant limitations to clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…With their well-known paracrine activity that promotes angiogenesis, enhances cell survival, and activates endogenous stem cells [3,4], methods that augment such paracrine activity with an aim to further the therapeutic potential of MSCs have also been investigated. For example, transplantation of MSCs overexpressing different angiogenic and cytoprotective factors, such as the stromal-derived factor-1 (SDF-1) [5], vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF) [6], angiopoietin-1 [7], and angiogenin (ANG) [8] significantly improve cardiac function through increased myocardial vascular density in animal models of myocardial infarction. In addition, targeting transcription factors, such as Akt-1 [9] and GATA-4 [10] that regulate the expression of multiple paracrine factors in MSCs, have also resulted in a significant increase in the in vitro production of various angiogenic and cytoprotective factors, and cardioprotection of the infarcted heart when the cells are implanted into the myocardium.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic Conditioning Enhances the Angiogenic Paracrine Activity of Human Adipose-Derived Stem Cells

Hsiao

Lokmic

Peshavariya

et al. 2013

Stem Cells and Development

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Human adipose-derived stem cells (ASCs) secrete cytokines and growth factors that can be harnessed in a paracrine fashion for promotion of angiogenesis, cell survival, and activation of endogenous stem cells. We recently showed that hypoxia is a powerful stimulus for an angiogenic activity from ASCs in vitro and here we investigate the biological significance of this paracrine activity in an in vivo angiogenesis model. A single in vitro exposure of ASCs to severe hypoxia ( < 0.1% O 2 ) significantly increased both the transcriptional and translational level of the vascular endothelial growth factor-A (VEGF-A) and angiogenin (ANG). The angiogenicity of the ASC-conditioned medium (ASC CM ) was assessed by implanting ASC CM -treated polyvinyl alcohol sponges subcutaneously for 2 weeks in mice. The morphometric analysis of anti-CD31-immunolabeled sponge sections demonstrated an increased angiogenesis with hypoxic ASC CM treatment compared to normoxic control ASC CM treatment (percentage vascular volume; 6.0% -0.5% in the hypoxic ASC CM vs. 4.1% -0.7% in the normoxic ASC CM , P < 0.05). Reduction of VEGF-A and ANG levels in the ASC CM with respective neutralizing antibodies before sponge implantation showed a significantly diminished angiogenic response (3.5% -0.5% in anti-VEGF-A treated, 3.2% -0.7% in anti-ANG treated, and 3.5% -0.6% in anti-VEGF-A/ANG treated). Further, both the normoxic and hypoxic ASC CM were able to sustain in vivo lymphangiogenesis in sponges. Collectively, the model demonstrated that the increased paracrine production of the VEGF-A and ANG in hypoxic-conditioned ASCs in vitro translated to an in vivo effect with a favorable biological significance. These results further illustrate the potential for utilization of an in vitro optimized ASC CM for in vivo angiogenesis-related applications as an effective cell-free technology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxic Conditioning Enhances the Angiogenic Paracrine Activity of Human Adipose-Derived Stem Cells

Hsiao

Lokmic

Peshavariya

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

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“…Similarly, the transplantation of adenovirus carrying human vascular endothelial growth factor 165 (Ad-hVEGF165) gene-transfected MSCs into rats with ischemic heart disease significantly promoted the host-derived angiogenesis and produced effective myogenesis as compared to MSCs transplant [133]. The transplantation of angiogenin-overexpressing human MSCs obtained after infection with adenovirus containing angiogenin gene (AdAng) also improved the heart perfusion and function in a porcine model of chronic ischemia as compared to MSC (AdNull) [134]. These treatment types, alone or in conjunction with the conventional medical therapies by using pharmaceutical agents such as angiotensinconverting enzyme (ACE) inhibitors, -adrenergic blockers, and nitroglycerin, should permit to improving the myocardiac regeneration and long-term outcome of patients diagnosed with heart failures resulting from ischemic heart disease, hypertension and myocardial infarction [9, 11, 16-18, 37, 128-131, 135].…”

Section: Cardiac Stem/progenitor Cells and Their Therapeutic Applicatmentioning

confidence: 99%

Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

2008

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Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibility to stimulate their in vivo differentiation or to use their ex vivo expanded progenies for cell replacement-based therapies with multiple applications in human. Among the human diseases that could be treated by the stem cell-based therapies, there are hematopoietic and immune disorders, multiple degenerative disorders, such as Parkinson's and Alzeimeher's diseases, type 1 or 2 diabetes mellitus as well as eye, liver, lung, skin and cardiovascular disorders and aggressive and metastatic cancers. In addition, the genetically-modified adult stem/progenitor cells could also be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues. Recent advances in cancer stem/progenitor cell research also offer the possibility to targeting these undifferentiated and malignant cells that provide critical functions in cancer initiation and progression and disease relapse for treating the patients diagnosed with the advanced and metastatic cancers which remain incurable in the clinics with the current therapies.

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“…MSC have been used as cellular delivery vehicles for anticancer agents or angiogenic factors in tumor or ischemic disease treatment, respectively. Increasing evidence indicates the advantages of this direct targeting therapy are its high efficacy, the low amount of systemic adverse side effects, and its safety [16,[19][20][21] . MSC would also be a suitable stem cell candidate for neovascular AMD treatment: (1) they make an important contribution to postnatal vasculogenesis [22] ; (2) they are simple to isolate and culture [19] , are accessible to genetic manipulation in vitro [23] , and have a high metabolic activity and efficient machinery for the secretion of therapeutic proteins [19] , and (3) they have a low intrinsic mutation rate [19] and low immunogenicity due to the lack of expression of costimulatory molecules [16] .…”

Section: Potential Application Of Bmc In the Anticipation And Treatmementioning

confidence: 99%

Bone Marrow-Derived Cells in Neovascular Age-Related Macular Degeneration: Contribution and Potential Application

Hou¹,

Liu

Wang³

2010

Ophthalmic Res

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Neovascular age-related macular degeneration, characterized by the formation of choroidal neovascularization (CNV), is a predominant cause of serious loss of vision. The pathogenesis of CNV is complex and still imperfectly understood. Prior studies have shown that bone marrow-derived cells (BMC) play a role in CNV. In this review article, we describe the contribution of BMC to CNV development, and discuss the potential use of BMC in the anticipation and treatment of CNV-associated diseases as well as research needs in the future.

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Transplantation of angiogenin-overexpressing mesenchymal stem cells synergistically augments cardiac function in a porcine model of chronic ischemia

Abstract: Transplantation of autologous mesenchymal stem cells transfected with the angiogenin gene revealed a synergistic effect on the improvement of heart perfusion and function after ameroid occlusion.

Cited by 33 publications

References 23 publications

Hypoxic Conditioning Enhances the Angiogenic Paracrine Activity of Human Adipose-Derived Stem Cells

Hypoxic Conditioning Enhances the Angiogenic Paracrine Activity of Human Adipose-Derived Stem Cells

Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

Bone Marrow-Derived Cells in Neovascular Age-Related Macular Degeneration: Contribution and Potential Application

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