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Filgrastim, fibrinolysis, and neovascularization
Darwin Eton1, Guolin Zhou2, Tong-Chuan He3
1Department of Surgery, University of Illinois Chicago, Chicago, Illinois, USA.
Journal of Tissue Engineering and Regenerative Medicine
|February 17, 2022
Summary
Filgrastim (a granulocyte colony stimulating factor) combined with a programmed compression pump (PCP) promotes artery recanalization in chronic limb-threatening ischemia (CLTI). This novel treatment induces fibrinolysis and a pro-angiogenic environment, warranting further clinical investigation.
Area of Science:
- Vascular Biology
- Regenerative Medicine
- Ischemia Research
Background:
- Chronic limb-threatening ischemia (CLTI) presents a significant challenge in vascular medicine.
- Current treatments for CLTI have limitations, necessitating novel therapeutic approaches.
- Understanding molecular mechanisms of neovascularization and fibrinolysis is crucial for improving CLTI outcomes.
Purpose of the Study:
- To investigate the effects of Filgrastim, a granulocyte colony stimulating factor, combined with a programmed compression pump (PCP) on segmental recanalization in CLTI patients.
- To explore the molecular evidence of fibrinolysis and neovascularization induced by this combined therapy.
- To assess the safety and efficacy of a novel Filgrastim dosimetry in CLTI.
Main Methods:
- A comparative study involving CLTI patients treated with PCP alone or with Filgrastim and PCP.
- Plasma and serum samples were analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) to measure plasmin, fibrin degradation products (FDP), and pro-angiogenic proteins (HGF, MMP-9, VEGF A).
- Blood draws were conducted at baseline and at specific time points following Filgrastim administration and PCP treatment.
Main Results:
- Filgrastim administration, independent of PCP, significantly increased plasma concentrations of plasmin (>10-fold) and FDP (>5-fold) after the 5th and 10th doses.
- Significant increases in pro-angiogenic proteins, including HGF, MMP-9, and VEGF A, were observed.
- The combined therapy demonstrated fibrinolysis and induced a pro-angiogenic milieu without causing acute hemorrhage.
Conclusions:
- Filgrastim at a novel dosimetry, in conjunction with PCP, effectively induces fibrinolysis and promotes a pro-angiogenic environment in CLTI patients.
- This therapeutic strategy shows potential for promoting neovascularization and artery recanalization in chronically ischemic tissues.
- Further clinical trials are warranted to validate this approach in CLTI and other ischemic conditions.
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