Muscle tissue stem cells could help prevent large number of diabetic amputations

by Barbara Hewitt on November 10, 2017

Stem cells taken from muscle tissue could promote better blood flow in people with diabetes who develop peripheral artery disease, a common and painful complication that can require surgery or lead to amputation.

New research in the United States has found that an injection of the stem cells prompted new blood vessels to grow in mice, improving circulation in the affected tissues and function in the affected limbs.

Stem Cells

(CI Photos/

The stem cells also induced changes in gene expression in the surrounding tissues, prompting the release of factors to reduce inflammation and increase circulation, according to the study by researchers at the University of Illinois.

Wawrzyniec Dobrucki, professor of bioengineering and medicine, explained that peripheral artery disease (PAD) is very common in diabetics but it is difficult to diagnose because patients experience symptoms when the disease is already at an advanced stage.

‘When the PAD is left untreated, it often leads to foot ulcerations and limb amputations. It’s a serious, costly and debilitating disease,’ he explained, adding that treatment options are limited.

In PAD, arteries in the limbs become narrowed, causing pain and limiting mobility due to lack of blood and oxygen. Some medications aim to increase perfusion in the limbs but are not very effective, according to Dobrucki.

He also pointed out that while doctors recommend exercise, it is often painful and difficult for PAD patients, and other cardiovascular complications may make physical activity impractical. Many patients require surgery to place vascular stents or an arterial bypass.

Dobrucki’s group along with Marni Boppart, a professor of kinesiology and community health, studied the effects of stem cells injected at the site where the artery narrows. Boppart is an expert in mesenchymal stem cells, which play a role in injury healing and tissue regeneration in muscle and other tissues.

The researchers surgically narrowed the femoral artery in one leg of diabetic mice. They injected MSCs, taken from the muscles of young mice, into the legs of the experimental mice, while the control group got a saline injection. Then they used non-invasive imaging techniques, developed in Dobrucki’s lab, to monitor blood flow and blood vessel formation in the mice, comparing both the experimental and control groups and the affected and non-affected legs in each mouse.

‘We clearly demonstrated the capacity for MSCs to increase angiogenesis, peripheral perfusion and muscle function. We saw that MSCs promoted muscle healing by creating new vessels in the tissue that compensated for restricted blood flow. MSC transplantation provides the opportunity to maximize vessel growth in PAD to maintain or rejuvenate skeletal muscle,’ Boppart said.

The researchers also performed an analysis of gene expression within the tissue and found that, in mice given the stem cell injections, the gene expression in the leg with PAD was close to that of the unaffected leg. They also found that, compared with the mice that did not get the stem cells, there were genes activated to combat some of the diabetic complications – for example, genes associated with inflammation were repressed.

‘Our results suggest that stem cell treatment could be used for those patients at severe stages of PAD who cannot exercise. Stem cell treatment could help bring them to the level where they can start exercising, or it could save an extremity before it needs amputation,’ Dobrucki said.

Next, the researchers are hoping to identify subpopulations of MSCs that demonstrate the most potential to treat PAD, as well as optimizing the conditions to isolate these rare cells from human fat tissue and skeletal muscle. They are also studying how long the MSCs stay active after injection, and what kind of immune response they may trigger.

‘We also are attempting to develop an acellular approach to rejuvenation of muscle repair and growth. We hope to identify the optimal composition of factors that the cells release, as well as the medium for release. Treatment with the right combination of factors, rather than the cells themselves, provides the opportunity to circumvent the potential for rejection by the immune system,’ Boppart added.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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