An Improved Stem Cell-Based Treatment for Peripheral Arterial Disease

by Adrienne Mueller, PhD
August 12, 2020

Peripheral arterial disease (PAD) is a significant disorder that affects over 10 million people in the United states. PAD is caused by a narrowing of the blood vessels in the arms and legs, often because of a build-up of fatty plaque in those vessels. This narrowing of the blood vessels reduces blood flow and that in turn can cause pain, difficulty using the affected limbs, and, in severe cases, lead to gangrene and subsequent amputation. You are at risk for PAD if you smoke, have diabetes, or are over 60 years of age. You also have an increased risk if you are African American or are of Hispanic descent. Currently, we treat PAD with surgical interventions, such as grafting vessels into the affected limb to try to restore blood flow. Unfortunately, many patients, especially those with severe forms of the disease, lack suitable vessels for this surgery. There is therefore a pressing need for alternative treatments. One of the most promising alternatives to surgery is the use of stem cells. Delivering stem cells into the affected limb could help regenerate new vessels to support blood flow. Stem cells grow well in low oxygen conditions, such as in tissue with reduced blood flow, and they secrete factors that promote the formation of new blood vessels.

One challenge holding back the deployment of stem cells to treat PAD is their poor initial survival when they are delivered into tissue. Therefore, a group of Stanford Cardiovascular Institute-affiliated scientists, including first author Caroline Hu and senior author Ngan Huang, PhD, recently investigated the use of a novel delivery mechanism: nanofibrillar scaffolds. Nanofibrillar scaffolds are a matrix of aligned collagen fibers that are thought to help cells survive by keeping stem cells organized and close to the site of delivery, as well as providing cues that promote survival. Hu et al wanted to determine whether nanofibrillar scaffolds were superior to the customary saline delivery vehicle in keeping transplanted stem cells alive and helping restore blood flow.

As their recent paper in Frontiers in Bioengineering and Biotechnology describes, the authors delivered a cocktail of stem cells into mice exhibiting PAD using either saline or nanofibrillar scaffolds as the vehicle. The researchers found that using nanofibrillar scaffolds to deliver stem cells into the limbs of PAD-like mice resulted in a significantly higher blood perfusion in the affected limbs compared to delivery with saline. Further, they found that even in culture, the stem cells plated with nanofibrillar scaffolds had six times higher secretion of growth factors – which promote cell growth and survival - than stem cells cultured with saline. This study therefore shows that using nanofibrillar scaffolds to deliver stem cells into tissue with reduced blood flow is an extremely promising method to improve stem cell-based treatments for PAD.

Blood flow is much higher in the limbs of mice that were injected with stem cells and nanofibrillar scaffolds compared to mice that were injected with stem cells and saline. A) These images show the lower limbs of PAD-like mice 14 days after stem cells were delivered with either saline or nanofibrillar scaffolds as the vehicle. B) Blood flow, quantified by mean perfusion ratio, in the affected limbs of mice treated with stem cells and saline or stem cells with nanofibrillar scaffolds at day 0 and day 14 post-treatment.

Other Stanford Cardiovascular Institute-affiliated authors include Cynthia Alcazar, Guang Yang, Mimi R. Borrelli, Derrick C. Wan, and Dung H. Nguyen.

Dr. Ngan Huang

Caroline Hu