Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

Zhang, J.C.; Zheng, Guo-Qing; Wu, Liang; Yang, Lan-Fang; Li, W.X.

doi:10.1590/1414-431x20143765

Cited by 22 publications

(10 citation statements)

References 38 publications

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“…These cells have been used in clinical trials to treat ischemic disease (Bura et al, 2014) and the safety of MSCs has been evaluated (Karussis et al, 2010;Lalu et al, 2012). To improve the effect of MSCs on ischemia-related disease, modified approaches such as over expression of angiogenesis-related genes such as bFGF on MSCs (Zhang et al, 2014), combination with other cells such as endothelial cells (Huang et al, 2013), antioxidants such as melatonin (Yip et al, 2013), serum deprivation , and cell spheroids (Park et al, 2014) have been developed.…”

Section: Enhanced Angiogenesis By Hypoxia Huc-mscsmentioning

confidence: 99%

Enhancement of angiogenic effects by hypoxia‐preconditioned human umbilical cord‐derived mesenchymal stem cells in a mouse model of hindlimb ischemia

Han

Kim

et al. 2015

Cell Biology International

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It has been studied that mesenchymal stem cells (MSCs) have the capability to promote angiogenesis. Furthermore, there is strong evidence that hypoxic conditions can enhance angiogenesis and immune modulation mediated by MSCs, a notion that has been applied in many fields of clinical application. In the present study, we compared the efficacy of hypoxia preconditioned human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and normoxia conditioned hUC-MSCs for the treatment of ischemic injury in hindlimbs of an immunodeficient mouse model. Expression of negative markers for MSC such as CD31, CD34, and CD45 or positive markers such as CD44, CD73, CD90, and CD105 was not significantly changed in hypoxia preconditioned hUC-MSCs compared with hUC-MSCs cultured in normoxic condition. Expression of angiogenesis-related genes such as COX-2, VEGF, Tie-2, and TGF-β1 was increased compared with hUC-MSCs cultured in normoxic conditions. In the in vivo model, CD31 expression as a marker of angiogenesis was significantly increased in the ischemic limbs at 1 month after injection with hypoxic hUC-MSCs. Angiogenesis-related genes such as Ang-1, COX-1, PIGF, and MCP-1 were significantly upregulated in the muscle of ischemic hindlimbs treated with hypoxic hUC-MSCs than normoxic hUC-MSCs. Expression of proinflammatory genes such as IL-1, and IL-20 was reduced, whereas TGF-β1, which has an anti-inflammatory effect, was strongly increased. In conclusion, hypoxic culture conditions could induce expression of angiogenesis related genes in hUC-MSCs, and hypoxia preconditioned hUC-MSCs showed enhancing effects by inducing angiogenesis and low inflammatory immune response compared with normoxic hUC-MSCs in the ischemia injured hindlimb of immunodeficient mice.

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Section: Enhanced Angiogenesis By Hypoxia Huc-mscsmentioning

confidence: 99%

Enhancement of angiogenic effects by hypoxia‐preconditioned human umbilical cord‐derived mesenchymal stem cells in a mouse model of hindlimb ischemia

Han

Kim

et al. 2015

Cell Biology International

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“…The use of HS on its own for the treatment of limb ischaemia is in contrast to studies investigating gene-, protein- or cell-based treatments for therapeutic angiogenesis in similar animal models [ 34 , 39 – 41 ]. The assumptions of such studies still rely on increasing the local concentration of angiogenic growth factors to stimulate neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate

Poon

Smith

et al. 2018

Angiogenesis

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Peripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF165) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF165. Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF165 against thermal and enzyme degradation in vitro, and isolated VEGF165 from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites.Electronic supplementary materialThe online version of this article (10.1007/s10456-018-9622-9) contains supplementary material, which is available to authorized users.

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“…These cells have been used in clinical trials to treat ischemic disease [74], and the safety of MSCs has been evaluated [129,130]. There are several modified approaches, which have been proposed to improve the effect of MSCs on ischemia-related disease, such as over expression of angiogenesis-related genes such as bFGF on MSCs [131], combination with other cells such as endothelial cells [84], antioxidants such as melatonin [132], serum deprivation [72], and cell spheroids [133].…”

Section: Hypoxic Mscs In Clinical Applicationmentioning

confidence: 99%

Hypoxia in Mesenchymal Stem Cell

Widowati¹,

Rihibiha²,

Khiong³

et al. 2017

Hypoxia and Human Diseases

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Mesenchymal stem cells (MSCs) are non-hematopoietic multipotent stem cells with selfrenewal properties and ability to differentiate into a variety of mesenchymal tissues. This chapter overviews effects of hypoxia on MSCs, makes it promising therapy to various diseases. Cultivation of MSCs under hypoxic condition results in variety of outcome that is important to be noted in clinical use. In most studies, hypoxic condition appears to increase proliferation, differentiation, and immune regulatory performance of MSCs without affecting its characteristic. Those benefits are therefore utilized in clinical application. However, there are also studies that report on negative effects of hypoxia in MSCs such as chromosomal instability. Molecular mechanism of MSCs in hypoxic condition is provided for better understanding, which is crucial for further development with better outcome.

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Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

Cited by 22 publications

References 38 publications

Enhancement of angiogenic effects by hypoxia‐preconditioned human umbilical cord‐derived mesenchymal stem cells in a mouse model of hindlimb ischemia

Enhancement of angiogenic effects by hypoxia‐preconditioned human umbilical cord‐derived mesenchymal stem cells in a mouse model of hindlimb ischemia

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate

Hypoxia in Mesenchymal Stem Cell

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