Exosomes Derived from Hypoxic Leukemia Cells Enhance Tube Formation in Endothelial Cells

Tadokoro, Hiroko; Umezu, Tomohiro; Ohyashiki, Kazuma; Hirano, Toshihiko; Ohyashiki, Junko H.

doi:10.1074/jbc.m113.480822

Cited by 320 publications

(287 citation statements)

References 36 publications

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“…Our flow cytometry detection showed that hucMSC-Ex were also positive for CD29 (data not shown). The effects of hucMSC-Ex on proliferation, migration, and tube formation of endothelial cells together contribute to new vessel formation [21]. Furthermore, our previous studies proved that hucMSC-Ex could alleviate liver fibrosis [15], protects against acute kidney injury [16], and enhance cutaneous wound closure [29].…”

Section: Discussionmentioning

confidence: 95%

“…Extracellular vesicles derived from human bone marrow mesenchymal stem cells could promote angiogenesis in tissue regeneration [17,18]. Exosomes enhance angiogenesis by delivering microRNAs, mRNAs, and active proteins [19][20][21][22][23][24]. We previously reported that exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) intensively enhance cutaneous wound healing; however, the effects of hucMSC-Ex on angiogenesis and the underlying mechanisms are not well characterized.…”

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confidence: 99%

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Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Zhang

et al. 2015

Stem Cells Translational Medicine

391

322

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Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted b-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and b-catenin and the decreased expression of E-cadherin. The activation of Wnt/b-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by b-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated b-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. STEM CELLS TRANSLATIONAL MEDICINE 2015; 4:513-522 SIGNIFICANCEHuman umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, it is reported that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be one of the important mechanisms responsible for cutaneous wound healing.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Zhang

et al. 2015

Stem Cells Translational Medicine

391

322

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“…Additionally, the involvement of vesicular miRNAs in neo-angiogenesis has been studied such as miRNA-210 that exhibited strong pro-angiogenic activity 22,40,83 . Furthermore, miRNA-210 has been observed to suppress the expression of specific genes such as EFNA3 (coding for Ephrin-A3) in endothelial cells, resulting in enhanced neo-angiogenesis 21,39,73 . Colorectal carcinoma cellsderived vesicular miRNA-9 shows pro-angiogenic effects through inhibiting the expression of suppressor of cytokine signaling 5 (SOCS 5), promoting the activation of the janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, a driver of endothelial cell migration 85 .…”

Section: Evs Set the Place And Time For Neo-angiogenesismentioning

confidence: 99%

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

et al. 2016

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“…Several studies demonstrate that small cellularly secreted vesicles called exosomes mediate much of MSCs' tissue healing capabilities [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. MSC derived exosomes are internalized by target cells and transfer proteins, RNA, lipids and metabolites [29].…”

Section: Phenotype Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell-based therapy for ischemic stroke

et al. 2016

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Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

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Exosomes Derived from Hypoxic Leukemia Cells Enhance Tube Formation in Endothelial Cells

Cited by 320 publications

References 36 publications

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

Mesenchymal stem cell-based therapy for ischemic stroke

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