Recruiting stem cells for blood vessel regeneration

Funding Type: 
Early Translational IV
Grant Number: 
TR4-06767
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Peripheral arterial disease (PAD) affects 10 million Americans and the prevalence is rising due to continued growth of diabetes and aging of the population, which may result in disabling pain, nonhealing wounds and limb amputation in the absence of successful revascularization. Nearly 100,000 major amputations are performed annually in the US due to PAD, the majority occurring in diabetes. Thus, there is a major unmet need for a small caliber bypass vascular graft to treat PAD. The objective of this Development Candidate Award is to engineer nanofibrous vascular grafts with bioactive molecule to recruit endogenous stem cells and progenitor cells that can differentiate into endothelial cells and smooth muscle cells to regenerate blood vessel in vivo. This approach is based on our understanding on stem cell biology and vascular biology during vascular regeneration. We will optimize and scale up the vascular graft production in a GMP-compatible manner, perform mechanistic studies in a rat model, and complete preliminary preclinical assessment of the development candidate in a large animal model. If successful, the development of bioactive vascular grafts will open a new avenue for vascular therapy and PAD treatment to avoid limb amputation and disability, which will benefit patients and healthcare.
Statement of Benefit to California: 
Peripheral arterial disease (PAD) affects 10 million Americans and the prevalence is rising due to continued growth of diabetes and aging of the population, which may result in disabling pain, nonhealing wounds and limb amputation in the absence of successful revascularization. Nearly 100,000 major amputations are performed annually in the US due to PAD, the majority occurring in diabetes. Thus, there is a major unmet need for a small caliber bypass vascular graft to treat PAD. Up to date, there is no effective therapy for PAD. Autologous grafts such as saphenous vein are either not available due to prior use or unsuitable for vascular reconstruction due to pre-existing disease in as many as 40% of patients, and synthetic grafts have high failure rate. The development of bioactive vascular grafts will allow us to treat PAD effectively, and benefit the patients and healthcare.

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