Transplantation of sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease

Piao, Wenhua; Wang, Huishan; Inoue, Makoto; Hasegawa, Mamoru; Hamada, Hirofumi; Huang, Jianhua

doi:10.1007/s10456-010-9169-x

Cited by 29 publications

(22 citation statements)

References 28 publications

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“…In the special case of ARS, this last point is not as critical because of the immunosup pression observed in these patients. Important for our approach, UCMSCs can be efficiently engi neered, thus holding great promise as vehicles for adult stem cell-based gene therapy [37][38][39], Addi tionally, UCMSCs can be expanded and manufac tured at industrial scale in a Good Manufacturing Practice facility, cryogenically frozen, and stored in Both pathways converge at the upregulation of pi 6 that induces senescence of HSCs. In addition, activation of p53 also induces the expression of various pro-apoptotic proteins to cause HSC apoptosis [43].…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase–expressing umbilical cord mesenchymal stromal cells

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase–expressing umbilical cord mesenchymal stromal cells

et al. 2015

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“…25 Moreover, MSCs promote lower limb perfusion and foot ulcer healing in patients with CLI, either given alone 26 or in combination with endothelial progenitor cells. 27 MSCs engineered with growth factors or antiapoptotic agents, including Akt, 28 adrenomedullin, 29 and angiopoietin, 30 showed incremental enhancements of therapeutic activity in models of ischemia. Likewise, intracoronary delivery of GLP-1-overexpressing MSCs induces substantial cardiac recovery in an acute myocardial infarction model.…”

Section: Discussionmentioning

confidence: 99%

Perivascular Delivery of Encapsulated Mesenchymal Stem Cells Improves Postischemic Angiogenesis Via Paracrine Activation of VEGF-A

Katare

Riu

Rowlinson

et al. 2013

ATVB

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Objective-To test the therapeutic activity of perivascular transplantation of encapsulated human mesenchymal stem cells (MSCs) in an immunocompetent mouse model of limb ischemia. Approach and Results-CD1 mice underwent unilateral limb ischemia, followed by randomized treatment with vehicle, alginate microbeads (MBs), MB-encapsulated MSCs (MB-MSCs), or MB-MSCs engineered with glucagon-like peptide-1. Treatments were applied directly in the perivascular space around the femoral artery. Laser Doppler and fluorescent microsphere assessment of blood flow showed a marked improvement of perfusion in the MB-MSCs and MBMSCs engineered with glucagon-like peptide-1 groups, which was associated with increased foot salvage particularly in MB-MSCs engineered with glucagon-like peptide-1-treated mice. Histological analysis revealed increased capillary and arteriole density in limb muscles of the 2 MSC groups. Furthermore, MB-MSCs engineered with glucagon-like peptide-1 and, to a lesser extent, MB-MSC treatment increased functional arterial collaterals alongside the femoral artery occlusion. Analysis of expressional changes in ischemic muscles showed that MB-MSC transplantation activates a proangiogenic signaling pathway centered on vascular endothelial growth factor A. In contrast, intramuscular MB-MSCs caused inflammatory reaction, but no improvement of reparative vascularization. Importantly, nonencapsulated MSCs were ineffective either by intramuscular or perivascular route. Conclusions-Perivascular delivery of encapsulated MSCs helps postischemic reperfusion. This novel biological bypass method might be useful in patients not amenable to conventional revascularization approaches.

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“…96 The delivery of angiopoietin-1 with a Sendai virus-based vector to MSCs increased the pAkt levels and resulted in increased angiogenesis. 97 Adrenomedullin, an activator of the PI3K/Akt pathway, was shown to increase angiogenesis when it was infused together with transplanted MSCs. 25 The effect of MSCs on endothelial cells with respect to angiogenesis was also demonstrated using conditioned medium from MSC cultures.…”

Section: The Pi3k/akt Pathway and Msc-induced Angiogenesismentioning

confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

206

161

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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Transplantation of sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease

Cited by 29 publications

References 28 publications

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase–expressing umbilical cord mesenchymal stromal cells

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase–expressing umbilical cord mesenchymal stromal cells

Perivascular Delivery of Encapsulated Mesenchymal Stem Cells Improves Postischemic Angiogenesis Via Paracrine Activation of VEGF-A

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

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