Combining angiogenic gene and stem cell therapies for myocardial infarction

Pons, Jennifer; Huang, Yu; Takagawa, Junya; Arakawa-Hoyt, Janice; Ye, Jianqin; Grossman, William; Kan, Yuet Wai; Su, Hua

doi:10.1002/jgm.1362

Cited by 44 publications

(50 citation statements)

References 42 publications

(46 reference statements)

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“…There are many studies on combining MSCs and VEGF gene therapy for protecting neurons against hypoxic ischemic injury ), promoting MSC proliferation (Crespo-Diaz et al 2011, enhancing the efficacy of MSCs in the swine model of myocardial infarction (Liu et al 2009) and promoting cardiac function and MSC survival (Pons et al 2009). Some studies have shown that MSCs could also achieve the biological effects by secreting VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…The family of vascular endothelial growth factor (VEGF) molecules are potent initiators and regulators of angiogenesis with VEGF 165 being the most powerful and widely distributed within the body for promoting angiogenesis (Neufeld et al 1999;Zhao et al 2007). BMMSCs transfected with the VEGF gene have been used in the treatment of cardiovascular disease (Liu et al 2009;Pons et al 2009;Zisa et al 2009), bone regeneration , neurodegenerative , and Achilles tendon repair (Hou et al 2009). However, there has not been research on VEGF gene modified BMMSCs and its role in the liver disease process.…”

Section: Introductionmentioning

confidence: 99%

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VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

Yan

Xiao

et al. 2012

Cytotechnology

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A short half-life and low levels of growth factors in an injured microenvironment necessitates the sustainable delivery of growth factors and stem cells to augment the regeneration of injured tissues. Our aim was to investigate the ability of VEGF 165 expressing bone marrow mesenchymal stem cells (BMMSCs) to differentiate into hepatocytes when cultured with hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in vitro. We isolated, cultured and identified rabbit BMMSCs, then electroporated the BMMSCs with VEGF 165 -pCMV6-AC-GFP plasmid. G418 was used to select transfected cells and the efficiency was up to 70%. The groups were then divided as follows: Group A was electroporated with pCMV6-AC-GFP plasmid ? HGF ? EGF and Group B was electroporated with VEGF 165 -pCMV6-AC-GFP plasmid ?HGF ? EGF. After 14 days, BMMSCs were induced into short spindle and polygonal cells. Alpha-fetoprotein (AFP) was positive and albumin (ALB) was negative in Group A, while both AFP and ALB were positive in group B on day 10. AFP and ALB in both groups were positive on day 20, but the quantity of AFP in group B decreased with prolonged time and was about 43.5% less than group A. The quantity of the ALB gene was increased with prolonged time in both groups. However, there was no significant difference between group A and B on day 10 and 20. Our results demonstrated that VEGF 165 -pCMV6-AC-GFP plasmid modified BMMSCs still had the ability to differentiate into hepatocytes. The VEGF 165 gene promoted BMMSCs to differentiate into hepatocyte-like cells under the induction of HGF and EGF, and reduced the differentiation time. These results have implications for cell therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

Yan

Xiao

et al. 2012

Cytotechnology

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“…Cytokines secreted by solid tumours have been shown to exert a positive chemotactic effect on mesenchymal stem cells. Thanks to that, these cells might be used as vectors transporting cytotoxic agents (granzymes, perforin, granulysin, cathepsins, TIA-1) that induce apoptosis in tumour cells and locally release high levels of cytokines that stimulate stronger immune responses [48,49]. This property of mesenchymal stem cells also allows attempts to modify the cell genome in order to enhance the cellular expression of interferon γ, IL-12, and many other substances that accelerate cancer cell destruction.…”

Section: Novel Cancer Stem Cell-targeting Therapymentioning

confidence: 99%

Cancer stem cells – a new chance for successful treatment of cancer

Badowska-Kozakiewicz¹,

Budzik²

2015

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Cancer stem cells are undifferentiated cells capable of being transformed into all types of cells comprising the tumour mass. As demonstrated by recent findings, they are responsible for the development of both haematopoietic malignancies and solid lesions. Cancer stem cells determine the unlimited growth of tumours and the variety of their morphology; they are also suspected of being the factor responsible for metastases. Their capability for renewal is the cause of disease recurrences even after long remission periods. Studies have shown that cancer stem cells may develop from normal stem cells, mature cells, and differentiated, or already transformed cells. What differentiate these cells from other cancer cells are rare mitotic divisions, which play a protective role for the cancer genome. StreszczenieNowotworowe komórki macierzyste to niezróżnicowane komórki zdolne do przekształcania się we wszystkie typy komórek budujących masę nowotworu. Jak się okazało w ostatnich latach, odpowiedzialne są zarówno za rozwój nowotworów układu krwiotwórczego, jak i powstawanie zmian litych. To właśnie te komórki warunkują nieograniczony wzrost nowotworów, ich różnorodność w budowie morfologicznej oraz -jak się przypuszcza -są czynnikiem powodującym powstawanie przerzutów. Ich zdolność do odnowy jest przyczyną nawrotów choroby, nawet po dłuższych okresach remisji. Wyniki badań wykazały, że nowotworowe komórki macierzyste mogą się rozwijać z prawidłowych komórek macierzystych, komórek dojrzałych, zróżnicowanych oraz komórek już transformowanych nowotworowo. Cechą wyróżniającą nowotworowe komórki macierzyste, w odróżnieniu od pozostałych komórek nowotworowych, są rzadkie podziały mitotyczne, pełniące funkcję ochronną dla genomu komórek nowotworu. Stem cellsNormal stem cells (NSC) are relatively non-specialised cells capable of division leading to identical offspring cells (self-renewal potential), as well as differentiation into one or more types of specialised cells in particular conditions (differentiation potential). This distinguishes these cells from other cells of the human body, which die after reaching their division limit.Stem cell divisions can be classified into two types: symmetric division leading to two stem cells that maintain the traits of the parent cell; and asymmetric division, leading to one stem cell identical to the parent cell and another one that undergoes differentiation or, in particular conditions, apoptosis [1]. Stem cells collected from blastocyst embryos are capable of differentiating into any type of systemic cells; these are referred to as embryonic stem cells. Stem cells are also present in mature organisms; they are known as somatic or adult stem cells. However, they are capable of differentiating only into some types of specialised cells. Although the quantity of NSCs in the human body is very low (they account for less than one per million of all body cells), ongoing studies have allowed us to isolate and multiply these cells with ever increasing efficacy while offering chances for b...

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“…Therefore, the mechanisms leading to stem/progenitor cell dysfunction need to be better characterized and will provide interesting novel approaches to optimize cellbased treatment approaches. Moreover, strategies to improve cardiac homing and engraftment of stem/progenitor cells may optimize the effect the results of this treatment approach (Pons et al 2008;Pons et al 2009;Tang et al 2009;Zhao et al 2009).…”

Section: Future Directions Of Cell Based-therapy For Ischemic Heart Dmentioning

confidence: 99%

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

Templin¹,

Lüscher²,

Landmesser³

2011

Int. J. Dev. Biol.

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Ischemic heart disease is the main cause of death and morbidity in most industrialized countries. Stem-and progenitor cell-based treatment approaches for ischemic heart disease are therefore an important frontier in cardiovascular and regenerative medicine. Experimental studies have shown that bone-marrow-derived stem cells and endothelial progenitor cells can improve cardiac function after myocardial infarction, clinical phase I and II studies were rapidly initiated to translate this concept into the clinical setting. However, as of now the effects of stem/ progenitor cell administration on cardiac function in the clinical setting have not met expectations. Thus, a better understanding of causes of the current limitations of cell-based therapies is urgently required. Importantly, the number and function of endothelial progenitor cells is reduced in patients with cardiovascular risk factors and/or coronary artery disease. These observations may provide opportunities for an optimization of cell-based treatment approaches. This review provides a summary of current evidence for the role and potential of stem and progenitor cells in the pathophysiology and treatment of ischemic heart disease, including the properties, and repair and regenerative capacities of various stem and progenitor cell populations. In addition, we describe modes of stem/progenitor cell delivery, modulation of their homing as well as potential approaches to "prime" stem/progenitor cells for cardiovascular cell-based therapies.

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Combining angiogenic gene and stem cell therapies for myocardial infarction

Abstract: Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

Cited by 44 publications

References 42 publications

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

Cancer stem cells – a new chance for successful treatment of cancer

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

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