Effects of calcium and thrombin on growth factor release from platelet concentrates: Kinetics and regulation of endothelial cell proliferation

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

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Requirement for Protein Kinase C Activation in Basic Fibroblast Growth Factor–Induced Human Endothelial Cell Proliferation

Circulation Research ◽

10.1161/01.res.77.2.231 ◽

1995 ◽

Vol 77 (2) ◽

pp. 231-238 ◽

Cited By ~ 47

Author(s):

K. Craig Kent ◽

Shinsuke Mii ◽

Elizabeth O. Harrington ◽

James D. Chang ◽

Sheila Mallette ◽

...

Keyword(s):

Cell Proliferation ◽

Protein Kinase C ◽

Endothelial Cell ◽

Growth Factor ◽

Protein Kinase ◽

Fibroblast Growth Factor ◽

Endothelial Cell Proliferation ◽

Fibroblast Growth ◽

Kinase C ◽

Protein Kinase C Activation

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Endostatin: A Promising Drug for Antiangiogenic Therapy

The International Journal of Biological Markers ◽

10.1177/172460089901400412 ◽

1999 ◽

Vol 14 (4) ◽

pp. 263-267 ◽

Cited By ~ 13

Author(s):

L. Cirri ◽

S. Donnini ◽

L. Morbidelli ◽

P. Chiarugi ◽

M. Ziche ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Growth Factor ◽

Antiangiogenic Therapy ◽

Specific Inhibitor ◽

Angiogenesis Inhibitors ◽

Endothelial Cell Proliferation ◽

Platelet Factor ◽

Collagen Xviii ◽

And Migration

Angiogenesis, the formation of new blood vessels from existing capillaries, is critical for tumors to grow beyond a few in size. Tumor cells produce one or more angiogenic factors including fibroblast growth factor and vascular endothelial growth factor. Surprisingly, antiangiogenic factors or angiogenesis inhibitors have been isolated from tumors. Some angiogenesis inhibitors, such as angiostatin, are associated with tumors while others, such as platelet-factor 4 and interferon-alpha are not. Endostatin, a C-terminal product of collagen XVIII, is a specific inhibitor of endothelial cell proliferation, migration and angiogenesis. The mechanism by which endostatin inhibits endothelial cell proliferation and migration is unknown. Endostatin was originally expressed in a prokaryotic system and, late, in a yeast system, thanks to which it is possible to obtain a sufficient quantity of the protein in a soluble and refolded form to be used in preclincial and clinical trials.

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Monocyte activation state regulates monocyte-induced endothelial proliferation through Met signaling

Blood ◽

10.1182/blood-2009-02-207340 ◽

2010 ◽

Vol 115 (16) ◽

pp. 3407-3412 ◽

Cited By ~ 10

Author(s):

Shai Y. Schubert ◽

Alejandro Benarroch ◽

Juan Monter-Solans ◽

Elazer R. Edelman

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Endothelial Cell ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Direct Interaction ◽

Endothelial Cell Proliferation ◽

Specific Cell ◽

Mrna Levels ◽

Hepatocyte Growth

Abstract Direct interaction of unactivated primary monocytes with endothelial cells induces a mitogenic effect in subconfluent, injured endothelial monolayers through activation of endothelial Met. We now report that monocytes' contact-dependent mitogenicity is controlled by activation-mediated regulation of hepatocyte growth factor. Direct interaction of unactivated monocytes with subconfluent endothelial cells for 12 hours resulted in 9- and 120-fold increase in monocyte tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) mRNA levels and bitemporal spike in hepatocyte growth factor that closely correlates with endothelial Met and extracellular signal-related kinase (ERK) phosphorylation. Once activated, monocytes cannot induce a second wave of endothelial cell proliferation and endothelial Met phosphorylation and soluble hepatocyte growth factor levels fall off. Monocyte-induced proliferation is dose dependent and limited to the induction of a single cell cycle. Monocytes retain their ability to activate other endothelial cells for up to 8 hours after initial interaction, after which they are committed to the specific cell. There is therefore a profoundly sophisticated mode of vascular repair. Confluent endothelial cells ensure vascular quiescence, whereas subconfluence promotes vessel activation. Simultaneously, circulating monocytes stimulate endothelial cell proliferation, but lose this potential once activated. Such a system provides for the fine balance that can restore vascular and endothelial homeostasis with minimal overcompensation.

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