HYBRID EVENT: You can participate in person at London, UK or Virtually from your home or work.

5th Edition of International Conference on Tissue Engineering and Regenerative Medicine

September 18-20 | London, UK

September 18 -20, 2025 | London, UK
TERMC 2025

Progenitor cell mobilization and induced neutrophilia promote neovascularization and fibrinolysis in chronically ischemic tissue

Darwin Eton, Speaker at Regenerative Medicine Conferences
Vasogenesis Inc, United States
Title : Progenitor cell mobilization and induced neutrophilia promote neovascularization and fibrinolysis in chronically ischemic tissue

Abstract:

A quarter of a century ago Granulocyte Colony Stimulating Factor (G-CSF) was used to induce progenitor cell mobilization in clinical trials so as to promote neovascularization in patients with chronic ischemia, both in the heart and in patients with chronic limb threatening ischemia (CLTI). At that time, the associated induced significant neutrophilia was considered anti-angiogenic and pro-thrombotic. However recent evidence has identified the context dependent role of neutrophils in modulating both angiogenesis and fibrinolysis. The pro-angiogenic impact of activated neutrophils includes the release of Hepatocyte Growth Factor, VEGF-A, MMP-9, and angiopoietin 1. Moreover, neutrophils secrete proteases that degrade thrombus and have context-dependent fibrinolytic capacity.

Proteomic and cytometry data were obtained a day after the fifth and tenth doses of G-CSF in a CLTI population treated with a novel G-CSF regimen (Filgrastim 7-10 mcg/kg every 72 hours for up to 10 doses). Enzyme-linked Immunosorbent assays identified significant (p<0.01) elevation of the concentration pro-angiogenic serum proteins (Hepatocyte Growth Factor, VEGF-A, MMP-9, and others) and of the pro-fibrinolytic plasma protein plasmin (>10-fold), as well as evidence of fibrinolysis as measured by the increase in Fibrin Degradation Products (>5-fold) in plasma . Levels peaked one day after each G-CSF dose, as did the absolute neutrophil count (ANC). Levels decreased toward baseline before the next dose, in conjunction with the ANC. No hemorrhage occurred during the month of G-CSF treatment. Angiographic evidence of both neovascularization and fibrinolysis was observed in these CLTI patients. These explained the improved arterial hemodynamics and the improved clinical course. The significance of this study is reflected in the use of ELISA and cytometry to inform dosimetry, which was lacking in previous G-CSF trials.

Conclusion: Clinical evidence supports a new hypothesis that both Induced neutrophilia and progenitor cell mobilization can promote a pro-angiogenic and pro-fibrinolytic environment in the context of chronically ischemic tissue. This potentially transformative cell therapy supports further investigation into a durable tissue level revascularization approach that could evolve into first line therapy, deferring or obviating the need for invasive large artery revascularization to manage chronically ischemic tissue.

Biography:

Dr Darwin Eton is a Distinguished Fellow of the Society of Vascular Surgery. He graduated from the Massachusetts Institute of Technology (B.Sc, MSc.) in 1978 and New York University Medical School (M.D.) in 1982. He initiated this project in 1999 at University of Miami where he was Professor and Chief of Vascular Surgery. He continued the clinical work as Professor of Surgery at the University of Chicago. This project won the Cures Within Reach Award in 2016. The proceeds were used to fund a confirmatory study at University of Illinois at Chicago, where Dr Eton had a Voluntary Professor appointment in Surgery. He started Vasogenesis Inc (Boston MA), where he presently serves as the Chief Research and Medical Officer. He has authored 45 peer review publications, book chapters, and books in Vascular Surgery, and has been an invited speaker in USA and internationally.

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