Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing

Abstract Background Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated. Methods The potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model. Results XF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization. Conclusions Here, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.

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Enhanced In Vivo Bone and Blood Vessel Formation by Iron Oxide and Silica Doped 3D Printed Tricalcium Phosphate Scaffolds

Annals of Biomedical Engineering ◽

10.1007/s10439-018-2040-8 ◽

2018 ◽

Vol 46 (9) ◽

pp. 1241-1253 ◽

Cited By ~ 22

Author(s):

Susmita Bose ◽

Dishary Banerjee ◽

Samuel Robertson ◽

Sahar Vahabzadeh

Keyword(s):

Iron Oxide ◽

Blood Vessel ◽

Tricalcium Phosphate ◽

Blood Vessel Formation ◽

Vessel Formation ◽

3D Printed

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Defibrotide, an Endothelium Protecting and Stabilizing Drug, Has Anti-Angiogenic Potential In Vitro and In Vivo.

Blood ◽

10.1182/blood.v106.11.3956.3956 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3956-3956

Author(s):

Guenther Eissner ◽

Edward K. Geissler ◽

Massimo Iacobelli ◽

Reinhard Andreesen ◽

Ernst Holler ◽

...

Keyword(s):

Blood Vessel ◽

Tube Formation ◽

Blood Levels ◽

Human Gastric Cancer ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Tumor Blood Vessel ◽

Skin Fold

Abstract DF is a polydisperse mixture of single-stranded polydeoxyribunucleotides which is successfully used in the treatment of hepatic veno-occlusive disease and other endothelial disorders. Recent pre-clinical evidence suggests that DF might also have anti-neoplastic properties. We addressed the question whether this might be due to the prevention of tumor blood vessel formation (angiogenesis). The anti-angiogeneic potential of DF was tested in vitro (Matrigel™ tube formation and aortic ring assay) and in vivo (dorsal skin-fold chamber model). Our results show that DF quantitatively (100%) blocks tube formation of trans-differentiated human endothelial-like cells (ELC) at concentrations corresponding to pharmacologic DF blood levels (100 μg/mL). Similarly, the sprouting of rat aorta endothelial cells in Matrigel™ was prevented by nearly 100%, when DF was applied on a daily basis. In vivo tumor angiogenesis in a human gastric cancer (TMK-1) grown in skin-fold chambers (nude mice) was also attenuated on day 5 by DF, as measured by microvascular density. Although the exact mechanism of DF action remains to be elucidated, initial Western blotting results show that DF reduces phosphorylation-activation of p70S6 kinase, which is a key target in the PI3K/Akt/mTOR signaling pathway linked to endothelial cell and pericyte proliferation and activation. Taken together, our data suggest that while DF is known for its endothelium-protecting function, it also inhibits tumor blood vessel formation, and thus should be considered for further testing as an anticancer agent.

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ANGPTL3 Stimulates Endothelial Cell Adhesion and Migration via Integrin αvβ3 and Induces Blood Vessel Formation in Vivo

Journal of Biological Chemistry ◽

10.1074/jbc.m109768200 ◽

2002 ◽

Vol 277 (19) ◽

pp. 17281-17290 ◽

Cited By ~ 146

Author(s):

Gieri Camenisch ◽

Maria Teresa Pisabarro ◽

Daniel Sherman ◽

Joe Kowalski ◽

Mark Nagel ◽

...

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Blood Vessel ◽

Integrin Αvβ3 ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Cell Adhesion And Migration ◽

And Migration ◽

Endothelial Cell Adhesion

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Fucoidan from Fucus vesiculosus inhibits new blood vessel formation and breast tumor growth in vivo

Carbohydrate Polymers ◽

10.1016/j.carbpol.2019.115034 ◽

2019 ◽

Vol 223 ◽

pp. 115034 ◽

Cited By ~ 10

Author(s):

Catarina Oliveira ◽

Sara Granja ◽

Nuno M Neves ◽

Rui L Reis ◽

Fátima Baltazar ◽

...

Keyword(s):

Blood Vessel ◽

Tumor Growth ◽

Breast Tumor ◽

Fucus Vesiculosus ◽

Blood Vessel Formation ◽

Vessel Formation

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Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation

Blood ◽

10.1182/blood-2006-07-037952 ◽

2006 ◽

Vol 109 (4) ◽

pp. 1345-1352 ◽

Cited By ~ 77

Author(s):

Gefei Zeng ◽

Sarah M. Taylor ◽

Janet R. McColm ◽

Nicholas C. Kappas ◽

Joseph B. Kearney ◽

...

Keyword(s):

Cell Division ◽

Endothelial Cell ◽

Blood Vessel ◽

Embryonic Stem ◽

Es Cell ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Vegf Signaling ◽

Vascular Beds

Abstract New blood vessel formation requires the coordination of endothelial cell division and the morphogenetic movements of vessel expansion, but it is not known how this integration occurs. Here, we show that endothelial cells regulate division orientation during the earliest stages of blood vessel formation, in response to morphogenetic cues. In embryonic stem (ES) cell–derived vessels that do not experience flow, the plane of endothelial cytokinesis was oriented perpendicular to the vessel long axis. We also demonstrated regulated cleavage orientation in vivo, in flow-exposed forming retinal vessels. Daughter nuclei moved away from the cleavage plane after division, suggesting that regulation of endothelial division orientation effectively extends vessel length in these developing vascular beds. A gain-of-function mutation in VEGF signaling increased randomization of endothelial division orientation, and this effect was rescued by a transgene, indicating that regulation of division orientation is a novel mechanism whereby VEGF signaling affects vessel morphogenesis. Thus, our findings show that endothelial cell division and morphogenesis are integrated in developing vessels by flow-independent mechanisms that involve VEGF signaling, and this cross talk is likely to be critical to proper vessel morphogenesis.

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The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis

Blood ◽

10.1182/blood-2003-07-2315 ◽

2004 ◽

Vol 103 (12) ◽

pp. 4527-4535 ◽

Cited By ~ 146

Author(s):

Joseph B. Kearney ◽

Nicholas C. Kappas ◽

Catharina Ellerstrom ◽

Frank W. DiPaola ◽

Victoria L. Bautch

Keyword(s):

Blood Vessel ◽

Fluorescent Protein ◽

Time Lapse ◽

Branching Morphogenesis ◽

Soluble Form ◽

Vegf Receptor ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Sprout Formation

Abstract Sprouting angiogenesis is critical to blood vessel formation, but the cellular and molecular controls of this process are poorly understood. We used time-lapse imaging of green fluorescent protein (GFP)-expressing vessels derived from stem cells to analyze dynamic aspects of vascular sprout formation and to determine how the vascular endothelial growth factor (VEGF) receptor flt-1 affects sprouting. Surprisingly, loss of flt-1 led to decreased sprout formation and migration, which resulted in reduced vascular branching. This phenotype was also seen in vivo, as flt-1-/- embryos had defective sprouting from the dorsal aorta. We previously showed that loss of flt-1 increases the rate of endothelial cell division. However, the timing of division versus morphogenetic effects suggested that these phenotypes were not causally linked, and in fact mitoses were prevalent in the sprout field of both wild-type and flt-1-/- mutant vessels. Rather, rescue of the branching defect by a soluble flt-1 (sflt-1) transgene supports a model whereby flt-1 normally positively regulates sprout formation by production of sflt-1, a soluble form of the receptor that antagonizes VEGF signaling. Thus precise levels of bioactive VEGF-A and perhaps spatial localization of the VEGF signal are likely modulated by flt-1 to ensure proper sprout formation during blood vessel formation. (Blood. 2004;103:4527-4535)

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