Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo

Gluzman, Zoya; Koren, Belly; Preis, Meir; Cohen, Tzafra; Tsaba, Adili; Cosset, François‐Loïc; Shofti, Rona; Lewis, Basil S.; Virmani, Renu; Flugelman, Moshe Y.

doi:10.1016/j.bbrc.2007.05.097

Cited by 24 publications

(32 citation statements)

References 24 publications

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“…Ang1-modified BMSCs increase angiogenesis and arteriogenesis 21. Autologous secretion of Ang1 by transduced ECs induces Tie-2 activation and promotes arteriogenesis after limb ischemia 22. Our data show that Isch-BMSC treatment of stroke increases Ang1 and Tie2 expression compared with Nor-BMSCs in the ischemic brain.…”

Section: Discussionmentioning

confidence: 73%

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Zacharek

Shehadah

Chen

et al. 2010

Stroke

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Background and Purpose-We compared the effect of treatment of stroke with bone marrow stromal cells from stroke rats (Isch-BMSC) and normal rats (Nor-BMSC) on functional outcome. Methods-Isch-BMSCs and Nor-BMSCs were intravenously injected into rats 24 hours after middle cerebral artery occlusion.To test the mechanism of Isch-BMSC-enhanced neurorestoration, Isch-BMSC and Nor-BMSC cultures were used. Results-Isch-BMSC significantly promoted functional outcome and enhanced angiogenesis, arterial density, and axonal regeneration compared with Nor-BMSC treatment animals. Isch-BMSCs exhibited increased Angiopoietin-1, Tie2, basic fibroblast growth factor, glial cell-derived neurotrophic factor, vascular endothelial growth factor, and

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Section: Discussionmentioning

confidence: 73%

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Zacharek

Shehadah

Chen

et al. 2010

Stroke

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“…Furthermore, IGF‐1 promotes muscle fiber regeneration; this phenomenon may be reflected in the findings of enhanced myogenesis after QQMNCTx. VEGF‐B and Angn‐1 were up‐regulated in QQMNCs, and they potentiate vascular survival and maturation relating to arteriogenesis induced by pericyte recruitment . However, expression of mRNA encoding VEGF‐A, one of the main proangiogenic growth factors, was not elevated, but rather reduced in QQMNCs, relative to PBMNCs.…”

Section: Discussionmentioning

confidence: 95%

“…Expression of genes encoding vascular regeneration factors, including VEGF‐B, angiopoietin‐1 (Ang‐1), leptin, IL‐8, IL‐10, and insulin‐like growth factor 1 (IGF‐1), was much higher in QQMNCs than in PBMNCs; the fold increases in QQMNCs versus PBMNCs were 4.2 for VEGF‐B, 2.4 for Ang‐1, 35.9 for leptin, 6.3 for IL‐8, 5.4 for IL‐10, and 21.2 for IGF‐1 (Figure A and B). Especially, VEGF‐B and Ang‐1 also induce vascular maturation, and IGF‐1 exerts myogenic potential …”

Section: Resultsmentioning

confidence: 99%

Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Promotes Endothelial Progenitor Cell Expansion and Phenotype Transition of Anti‐Inflammatory Macrophage and T Lymphocyte to Cells With Regenerative Potential

Masuda

Tanaka

Fujimura

et al. 2014

JAHA

178

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BackgroundCell‐based therapies involving mononuclear cells (MNCs) have been developed for vascular regeneration to treat ischemic diseases; however, quality control of therapeutic MNCs has not been evaluated. We investigated the therapeutic potential of peripheral blood (PB) MNCs, operated by recently developed quality and quantity (QQ) culture of endothelial progenitor cells (EPCs).Methods and ResultsPBs were collected from healthy volunteers; peripheral blood mononuclear cells (PBMNCs) isolated from these PBs were subjected to QQ culture for 7 days with medium containing stem cell factor, thrombopoietin, Flt‐3 ligand, vascular endothelial growth factor, and interleukin‐6. The resulting cells (QQMNCs) in EPC colony‐forming assay generated significantly more definitive EPC colonies than PBMNCs. In flow cytometry, macrophages and helper T lymphocytes of QQMNCs became phenotypically polarized into angiogenic, anti‐inflammatory, and regenerative subsets: classical M1 to alternative M2; T helper (Th)1 to Th2; angiogenic or regulatory T‐cell expansion. Quantitative real‐time polymerase chain reaction (qRT‐PCR) assay revealed the predominant proangiogenic gene expressions in QQMNCs versus PBMNCs. Using murine ischemic hindlimb models, the efficacy of QQMNC intramuscular transplantation (Tx) was compared to that of PBMNCTx, cultured “early EPC” Tx (eEPCTx), and granulocyte colony‐stimulating factor mobilized CD34+ cell Tx (GmCD34Tx). Laser Doppler imaging revealed the blood perfusion recovery in ischemic hindlimbs after QQMNCTx superior to after PBMNCTx and eEPCTx, but also earlier than after GmCD34Tx. Histological evaluations and qRT‐PCR assays in ischemic hindlimbs demonstrated that QQMNCTx, similarly to GmCD34Tx, enhanced angiovasculogenesis and myogenesis, whereas it preponderantly inhibited inflammation and fibrosis versus PBMNCTx and eEPCTx.ConclusionsQQ culture potentiates the ability of PBMNCs to promote regeneration of injured tissue; considering the feasible cell preparation, QQ culture‐treated PBMNCs may provide a promising therapeutic option for ischemic diseases.Clinical Trial RegistrationURL: irb.med.u-tokai.ac.jp/d/2/monthly/2010.html; IRB No.: 10R‐020.URL: irb.med.u-tokai.ac.jp/d/2/monthly/201312.html; IRB No.: 13R228.

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“…VEGF is a known angiogenic cytokine and binds to receptors on EPCs, leading to mobilization of EPCs from the bone marrow and their subsequent differentiation. VEGF is involved in vascular survival and maturation during angiogenesis . High levels of VEGF were found in keloids …”

Section: Discussionmentioning

confidence: 99%

“…VEGF is involved in vascular survival and maturation during angiogenesis. 20,21 High levels of VEGF were found in keloids. 13,22 The source of VEGF in keloids remains unknown.…”

Section: Comparison Of Angiogenic Activity In Cd34 + Cells Obtained Fmentioning

confidence: 99%

Keloid patients have higher peripheral blood endothelial progenitor cell counts and CD34⁺ cells with normal vasculogenic and angiogenic function that overexpress vascular endothelial growth factor and interleukin‐8

et al. 2019

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Background One suggested reason for aberrant wound healing in keloid scars is chronic inflammation of the dermis. We hypothesized that excessive blood vessel formation and high capillary density in keloid tissue is caused by dysfunction of endothelial progenitor cells. Methods We compared the number of circulating endothelial progenitor cells and vasculogenic and angiogenic capacity, as well as secretory function, of circulating CD34+ cells in keloid patients and healthy individuals. Results Compared to mononuclear cell cultures from healthy donors, cultures of peripheral blood mononuclear cells obtained from keloid patients showed a more than twofold increase in the number of peripheral blood EPCs (fibronectin‐adhering cells that phagocytized acetylated low‐density lipoprotein and bound Ulex europaeus agglutinin‐I lectin). However, there was no difference in colony‐forming ability and participation in in vitro angiogenesis between circulating CD34+ cells isolated from keloid patients and healthy individuals. This means that circulating CD34+/endothelial progenitor cells in keloid patients have normal vasculogenic and angiogenic function. However, CD34+ cells derived from keloid patients demonstrated a more than sevenfold expression of the interleukin‐8 gene and a more than fivefold expression of the vascular endothelial growth factor gene than CD34+ cells derived from healthy individuals. Conclusions These results support the role of vascular endothelial growth factor and interleukin‐8 in increased recruitment of endothelial progenitor cells in keloid patients.

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Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo

Cited by 24 publications

References 24 publications

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Promotes Endothelial Progenitor Cell Expansion and Phenotype Transition of Anti‐Inflammatory Macrophage and T Lymphocyte to Cells With Regenerative Potential

Keloid patients have higher peripheral blood endothelial progenitor cell counts and CD34⁺ cells with normal vasculogenic and angiogenic function that overexpress vascular endothelial growth factor and interleukin‐8

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Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo

Cited by 24 publications

References 24 publications

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Comparison of Bone Marrow Stromal Cells Derived From Stroke and Normal Rats for Stroke Treatment

Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Promotes Endothelial Progenitor Cell Expansion and Phenotype Transition of Anti‐Inflammatory Macrophage and T Lymphocyte to Cells With Regenerative Potential

Keloid patients have higher peripheral blood endothelial progenitor cell counts and CD34+ cells with normal vasculogenic and angiogenic function that overexpress vascular endothelial growth factor and interleukin‐8

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Keloid patients have higher peripheral blood endothelial progenitor cell counts and CD34⁺ cells with normal vasculogenic and angiogenic function that overexpress vascular endothelial growth factor and interleukin‐8