Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction

Chen, H. K.; Hung, Huei Fong; Shyu, Kou‐Gi; Wang, B. W.; Sheu, Joen‐Rong; Liang, Yao Jen; Chang, Chih Chuan; Kuan, Peiliang

doi:10.1111/j.1365-2362.2005.01565.x

Cited by 55 publications

(35 citation statements)

References 40 publications

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“…In this regard, CD34 ϩ hematopoietic progenitor cells have been shown to promote neovascularization in mice 29 and regeneration of the infarcted myocardium in rats. 3 In addition, purified human CD34 ϩ progenitor cells are known to improve cardiac function in mice 30 and in patients after myocardial infarction. 31,32 It is noteworthy that the highly proangiogenic cell population of EPCs coexpressing markers such as CD133 and flk1 can be isolated from CD34 ϩ hematopoietic progenitors.…”

Section: Org Frommentioning

confidence: 99%

The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration

Grote¹,

Salguero²,

Ballmaier³

et al. 2007

Blood

103

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IntroductionBone marrow-derived and circulating hematopoietic progenitor cells have been shown to contribute to cardiovascular tissue regeneration. 1,2 CD34 ϩ hematopoietic progenitor cells were widely and successfully used in different transplantation models, including myocardial regeneration. 3 A subset of circulating CD34 ϩ cellsexpressing markers such as CD133 and vascular endothelial growth factor (VEGF) receptor-2 (flk1)-are endothelial progenitor cells (EPCs) with the ability to differentiate into mature endothelial cells, thus contributing to re-endothelialization and neovascularization. 4 In contrast, the ability of hematopoietic cells to transdifferentiate into functional cardiomyocytes is controversial. [5][6][7][8] Moreover, enhanced angiogenesis in response to progenitor cells may be influenced mainly by the release of growth factors rather than by cellular differentiation. 9 CCN1 (formerly known as CYR61) is a cysteine-rich heparinbinding protein that is encoded by an immediate early gene and belongs to the novel CCN gene family (connective tissue growth factor [CTGF], cysteine-rich angiogenic protein 61 [CYR61], and nephroblastoma overexpressed [Nov]). 10 The expression of CCN1 is rapidly induced in response to growth factors. 11 CCN1 is expressed by all types of vascular cells, is associated with the extracellular matrix (ECM) and mediates cell adhesion, migration, proliferation and neovascularization through cell type-specific binding mainly to ␣ 6 ␤ 1 , ␣ M ␤ 2 , and ␣ V ␤ 3 integrins. 10,[12][13][14] It is noteworthy that CCN1-deficient mice suffer embryonic death as a result of placental vascular insufficiency and compromised vessel integrity because of impaired vessel bifurcations and impaired VEGF-C expression, establishing CCN1 as a novel and essential regulator of vascular development. 15 In addition, it has been shown recently that CCN1 is critically involved in cardiac development. 16 Besides its ability to promote tumor growth, 17 we recently reported that enhanced CCN1 expression is associated with several cardiovascular pathophysiologic settings, such as atherosclerotic plaque formation, 18 enhanced vascular mechanical stretch, 19 cardiac pressure overload, and ischemic cardiomyopathy. 20 Recent evidence suggested that CCN1 expression is induced in various cardiovascular disorders, suggesting a role for CCN1 in cellular and tissue self-renewal, potentially involving circulating progenitor cells. Because the impact of CCN1 on progenitor cells is largely unknown, we used circulating human bone marrow-derived CD34 ϩ cells to study CCN1 effects on migration, release of growth factors, endothelial proliferation and neovascularization, which are important for cardiovascular regeneration. Materials and methods ReagentsAll chemicals were obtained from Sigma (Taufkirchen, Germany) unless otherwise specified. All cell culture plates were from TTP (Trasadingen, Switzerland). RGD peptides (Arg-Gly-Asp) and GRGDSP peptides (GlyArg-Gly-Asp-Ser-Pro) were from Bachem (Weil am Rhein, Germany). Human ...

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Section: Org Frommentioning

confidence: 99%

The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration

Grote¹,

Salguero²,

Ballmaier³

et al. 2007

Blood

103

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“…37 The majority of reported studies using hUCB cells showed improvement in the outcomes. [18][19][20][21][22][23][24][25] Cardiac functional improvements were almost universally reported as evaluated by: increased ejection fraction; improved wall motion; lowered LV end-diastolic pressure; and increased cardiac contraction as determined by the maximum slope of LV pressure. [18][19][20][21][23][24][25] There were conflicting reports on the effects of stem cells on LV fractional shorting.…”

Section: Cardiovascular Diseasementioning

confidence: 99%

“…22,23 Improvements in myocardial perfusion, evaluated by increased capillary density, were repeatedly demonstrated as were reductions in infarct size and the number of apoptotic cells. [18][19][20][21][22][23][24][25] Retardation or reduction in LV remodelling were also reported. 18,21,22 Although the vast majority of studies showed positive outcomes, HLA matching and further study are still needed before UCB stem cell therapies can become safe and effective treatments in humans.…”

Section: Cardiovascular Diseasementioning

confidence: 99%

“…Another study evaluated the use of gene therapies in conjunction with UCB stem cell therapy. 24 CD34ϩ cells were transfected with AAV-Ang1 and/or AAV-VEGF 165. The gene-modified stem cells resulted in greater increases in capillary density and cardiac performance along with larger reduction in infarct size compared to CD34ϩ cell therapy alone.…”

Section: Cardiovascular Diseasementioning

confidence: 99%

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Human umbilical cord blood stem cells, myocardial infarction and stroke

2009

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-Myocardial infarction (MI) and stroke are the first and third leading causes of death in the USA accounting for more than 1 in 3 deaths per annum. Despite interventional and pharmaceutical advances, the number of people diagnosed with heart disease is on the rise. Therefore, new clinical strategies are needed. Cell-based therapy holds great promise for treatment of these diseases and is currently under extensive preclinical as well as clinical trials. The source and types of stem cells for these clinical applications are questions of great interest. Human umbilical cord blood (hUCB) appears to be a logical candidate as a source of cells. hUCB is readily available, and presents little ethical challenges. Stem cells derived from hUCB are multipotent and immunologically naive. Here is a critical literature review of the beneficial effects of hUCB cell therapy in preclinical trials.

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“…Originally it was targeted towards treatment of inheritable single-gene disorders caused due to an absent or defective gene. However, applications of gene therapy have expanded to include treatment of acquired and infectious diseases and exogenously administered genes now are used in a wide variety of applications including immunomodulation, genetic vaccination and genetic pharmacology [1][2][3][4][5][6].…”

Section: Gene Therapymentioning

confidence: 99%

Rationally Designed Synthetic Vectors for Gene Delivery

Rao¹,

Yadava²,

Hughes³

2007

TODDJ

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Vector development is one of the most important challenges facing the successful use of genes for treatment of diseases. Although chemically produced vectors offer distinct advantages over biological systems such as viruses, there are still some hurdles that have to be overcome before synthetic gene delivery vectors can be successfully implemented. This brief review discusses the biological barriers that limit current delivery strategies and reviews currently employed strategies for plasmid delivery. Nanoparticle-based gene delivery is reviewed along with methods for their characterization, physiochemical properties and toxicity. Finally a prospectus is provided for future development of an ideal synthetic gene delivery vector.

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Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction

Abstract: Combined therapy with human umbilical cord blood CD34(+) cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.

Cited by 55 publications

References 40 publications

The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration

The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration

Human umbilical cord blood stem cells, myocardial infarction and stroke

Rationally Designed Synthetic Vectors for Gene Delivery

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