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Investigating Angiogenesis on a Functional and Molecular Level by Leveraging the Scratch Wound Migration Assay and the Spheroid Sprouting Assay
Published on: May 31, 2024
Angiogenesis: bench to bedside, have we learned anything?
Seung Uk Lee1, Joanna J Wykrzykowska, Roger J Laham
1Cardiovascular Division, BIDMC/Harvard Medical School, Boston, Massachusetts 02215, USA.
Insights
Angiogenesis therapies show promise for ischemic cardiomyopathy but face challenges. A structured research model is proposed to overcome limitations and advance treatment for end-stage cardiac ischemia.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Molecular Biology
Background:
- End-stage ischemic cardiomyopathy is a growing concern with limited treatment options.
- Early angiogenesis therapy trials demonstrated potential, but later trials failed to confirm benefits of single growth factors.
- Challenges include complexity of angiogenesis, inadequate animal models for human ischemic myocardium, and controlling for placebo effects.
Purpose of the Study:
- To review the challenges in angiogenesis research and treatment strategy development for ischemic cardiomyopathy.
- To propose a structured model for future investigations into angiogenic therapies.
Main Methods:
- Review of existing literature on angiogenesis therapy for ischemic cardiomyopathy.
- Analysis of limitations in pre-clinical and clinical trial methodologies.
- Development of a proposed structured research model.
Main Results:
- Single growth factor angiogenesis treatments have not translated successfully to larger clinical trials.
- Significant hurdles exist in modeling human ischemic myocardium and controlling for placebo effects in clinical studies.
- Current outcomes assessment methods are inadequate for establishing efficacy.
Conclusions:
- Overcoming the complexities of angiogenesis research requires a more rigorous and structured approach.
- The proposed model offers a framework for future investigations to improve the success of angiogenic therapies.
- A regimented approach is essential for developing effective angiogenesis treatments for refractory cardiac ischemia.
Abstract:
End-stage ischemic cardiomyopathy patients are an ever-increasing group of coronary artery disease patients, often with no options in our current treatment armamentarium. Angiogenesis therapy pre-clinical and phase I clinical trials showed great promise, however, the benefits of single growth factor treatments have not been borne out in the larger phase II randomized trials. The complexity of angiogenesis process and the challenges in creating animal models to replicate and study this process in ischemic adult human myocardium have been major limitations to progress in this field. In addition failure to control for the powerful placebo effect in the clinical trials and inadequate methods of outcomes measures assessment have created difficult to overcome road blocks in establishing the efficacy of angiogenic strategies. Herein we review the challenges of angiogenesis research and development of treatment strategies. We also propose a structured model for further investigations of angiogenic therapies. The adherence to such a regimented approach as proposed here is, in our opinion, the only way to achieve success in angiogenesis approach development to treatment of patients with end-stage cardiac ischemia refractory to other established therapies.
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