Bone marrow derived stromal cells modified by adenovirus-mediated HIF-1α double mutant protect cardiac myocytes against CoCl2-induced apoptosis

Wang, Yesong; Sun, Aijiao; Xue, Jiaojie; Chen, Feng; Li, Jun; Wu, Juekan

doi:10.1016/j.tiv.2009.06.002

Cited by 11 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous references [46,47], our study showed that MSCs contribute to the angiogenesis and anti-apoptosis, which may be partly due to the MSC-dependent paracrine mechanism and their potential for trans-differentiation [48-51]. …”

Section: Discussionsupporting

confidence: 92%

Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction

Huang

Qian

et al. 2014

Stem Cell Res Ther

View full text Add to dashboard Cite

IntroductionMesenchymal stem cells (MSCs) have potential for the treatment of myocardial infarction. However, several meta-analyses revealed that the outcome of stem cell transplantation is dissatisfactory. A series of studies demonstrated that the combination of cell and gene therapy was a promising strategy to enhance therapeutic efficiency. The aim of this research is to investigate whether and how the combination of overexpression of hypoxia-inducible factor-1α (HIF-1α) and co-transplantation of mesenchymal stem cells can enhance cardiac repair in myocardial infarction.MethodsWe investigated the therapeutic effects of myocardial transfection of HIF-1α and co-transplantation of MSCs on cardiac repair in myocardial infarction by using myocardial transfection of HIF-1α via an adenoviral vector. Myocardial infarction was produced by coronary ligation in Sprague-Dawley (SD) rats. Animals were divided randomly into six groups: (1) HIF-1α + MSCs group: Ad-HIF-1α (6 × 109 plate forming unit) and MSCs (1 × 106) were intramyocardially injected into the border zone simultaneously; (2) HIF-1α group: Ad-HIF-1α (6 × 109 plate forming unit) was injected into the border zone; (3) HIF-1α-MSCs group: Ad-HIF-1α transfected MSCs (1 × 106) were injected into the border zone; (4) MSCs group: MSCs (1 × 106) were injected into the border zone; (5) Control group: same volume of DMEM was injected; (6) SHAM group. Cardiac performance was then quantified by echocardiography as well as molecular and pathologic analysis of heart samples in the peri-infarcted region and the infarcted region at serial time points. The survival and engraftment of transplanted MSCs were also assessed.ResultsMyocardial transfection of HIF-1α combined with MSC transplantation in the peri-infarcted region improved cardiac function four weeks after myocardial infarction. Significant increases in vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) expression, angiogenesis and MSC engraftment, as well as decreased cardiomyocyte apoptosis in peri-infarcted regions in the hearts of the HIF-1α + MSCs group were detected compared to the MSCs group and Control group.ConclusionsThese findings suggest that myocardial transfection of HIF-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in myocardial infarction, indicating the feasibility and preliminary safety of a combination of myocardial transfection of HIF-1α and MSC transplantation to treat myocardial infarction.

show abstract

Section: Discussionsupporting

confidence: 92%

Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction

Huang

Qian

et al. 2014

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…The effects of bone marrow-derived MSCs in protecting cardiomyocytes against ischemic/hypoxic injury might be related to a paracrine mechanism involving the release of a wide range of cytokines [36]. Bone marrow-derived stromal cells expressing an adenovirus-born active form of HIF-1a protect ischemic cardiomyocytes against CoCl 2 -induced apoptosis [36]. Treatment of bone marrow-derived angiogenic cells with dimethyloxalylglycine, an a-ketoglutarate antagonist that induces HIF-1a activity, has significant survival advantage under conditions of low O 2 and low pH ex vivo and in ischemic tissues [10].…”

Section: Discussionmentioning

confidence: 99%

Endothelial Progenitor Cells Derived from Wharton's Jelly of the Umbilical Cord Reduces Ischemia-Induced Hind Limb Injury in Diabetic Mice by Inducing HIF-1α/IL-8 Expression

Shen

Liang

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

Peripheral arterial diseases, the major complication of diabetes, can result in lower limb amputation. Since endothelial progenitor cells (EPCs) are involved in neovascularization, the aim of this study was to examine whether EPCs isolated from Wharton's jelly (WJ-EPCs) of the umbilical cord, a rich source of mesenchymal stem cells, could reduce ischemia-induced hind limb injury in diabetic mice. We evaluated the effects of WJ-EPC transplantation on hind limb injury caused by femoral artery ligation in mice with streptozotocin (STZ)-induced diabetes. We found that the ischemic hind limb in mice with STZ-induced diabetes showed decreased blood flow and capillary density and increased cell apoptosis and that these effects were significantly inhibited by an injection of WJ-EPCs. In addition, hypoxia-inducible factor-1a (HIF-1a) and interleukin-8 (IL-8) were highly expressed in transplanted WJ-EPCs in the ischemic skeletal tissues and were present at high levels in hypoxia-treated cultured WJ-EPCs. Moreover, incubation of the NOR skeletal muscle cell line under hypoxic conditions in conditioned medium from EPCs cultured for 16 h under hypoxic conditions resulted in decreased expression of pro-apoptotic proteins and increased expression of anti-apoptotic proteins. The inhibition of HIF-1a or IL-8 expression by EPCs using HIF-1a siRNA or IL-8 siRNA, respectively, prevented this change in expression of apoptotic-related proteins. Wharton's jelly in the umbilical cord is a valuable source of EPCs, and transplantation of these EPCs represents an innovative therapeutic strategy for treating diabetic ischemic tissues. The HIF-1a/IL-8 signaling pathway plays a critical role in the protective effects of EPCs in the ischemic hind limb of diabetic mice.

show abstract

“…[223] Specifically, previous studies have demonstrated that HIF-1 α can decrease apoptosis of rat cardiomyocytes following simulated ischemia-reperfusion injury by inducing multiple protective genes. [224] In agreement with these results, Wang and colleagues determined that co-culturing cardiomyocytes with engineered MSCs (wherein cobalt chloride (CoCl 2 ) was used to mimic hypoxic/ischemic conditions including generation of reactive oxygen species (ROS)) [225] increased expression of TGF- β 1 and Bcl-2, concomitant with a reduction in the expression of caspase-3, LDH release, and TUNEL-positive cardiomyocytes when compared to non-engineered MSC-cardiomyocyte co-culture and cardiomyocytes alone.…”

Section: Engineering Stem Cells For Tissue Regenerationmentioning

confidence: 99%

Engineering Stem Cells for Biomedical Applications

Yin

Han

Lee

2015

Adv Healthcare Materials

View full text Add to dashboard Cite

Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer.

show abstract

Bone marrow derived stromal cells modified by adenovirus-mediated HIF-1α double mutant protect cardiac myocytes against CoCl2-induced apoptosis

Cited by 11 publications

References 22 publications

Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction

Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction

Endothelial Progenitor Cells Derived from Wharton's Jelly of the Umbilical Cord Reduces Ischemia-Induced Hind Limb Injury in Diabetic Mice by Inducing HIF-1α/IL-8 Expression

Engineering Stem Cells for Biomedical Applications

Contact Info

Product

Resources

About