One of the challenges in diabetes health management is wound healing. People with uncontrolled diabetes may develop poor circulation so their wounds are slow to heal since it is difficult for the body to deliver the nutrients to the wounds. The disease can also cause neuropathy or nerve damage, affecting the process of wound healing. This means that a patient may already sustain trauma to their feet but they may not still be aware of that injury because the nerves in that area are damaged or numb.
Diabetic foot ulcers
Even to the present, diabetic foot ulcers (DFU) are a major healthcare concern as there are only limited effective therapies for it. The American Diabetes Association considers DFUs as some of the most common yet dangerous and costly complications of diabetes, affecting 15% of people with diabetes.
In the US alone, about 25 million people are living with diabetes and a quarter of them have chronic foot ulcers. About 30% of these will lead to amputation. What’s even more alarming is the projected five-year mortality rate (48%) of people who undergo amputation, a statistic that is equal to colon cancer. A closer look at mortality after lower extremity amputation will lead experts to ask whether we are saving lives by preventing major amputation or are we hastening the death of patients with diabetes.
The cost burden of DFUs on US healthcare is over $43 billion a year however these expenditures are only good for standard care, including strict diet, surgery or antibiotics, and off-loading pressure from the foot to promote wound healing. The standard of care is helpful but still would result in healing only 30% of affected patients.
Mesenchymal stem cell-based therapy
Findings by the University of California-Davis scientists now show promise that a combination of glaucoma drug and stem cells can promote diabetic wound healing in mice. Their study focused on mesenchymal stem cells (MSCs), which are commonly used by researchers in the fields of tissue engineering and regenerative medicine to reconstruct previously damaged tissue.
Jan Nolta, Ph.D. from the Stem Cell Program at UC Davis told Genetic Engineering & Biotechnology News (GEN) that what propelled him to work on this health problem is to treat and heal the patients. The rather poor cure rate has likewise prompted vigorous studies for therapeutic alternatives to DFUs.
MSC-based treatment options to DFUs
While the Food and Drug Administration has already approved some cellular therapies for treating DFUs, the healing rates show only modest improvement when compared to the standard of care established for DFU. Dr. Nolta and the team also observed that none of these products are primarily composed of mesenchymal stem cells. They believe that MSC-based therapies are promising as treatment options to diabetic foot ulcers because of the beneficial effects of angiogenesis, immunomodulation, and other paracrine effects.
Previous research by the UC Davis team demonstrated that 85% of MSCs applied to scaffolds – materials engineered to cause desirable cellular interactions to contribute to the formation of new functional tissues – localize to the seeding side and are viable in culture for 15 days. A localization process at the cellular level takes place when a cellular entity or a substance is transported or maintained in a certain location within the membrane of the cell. Their work also showed hypoxia pre-treatment (depriving MSCs of oxygen) increased the survival of cells and enhanced their retention at the wound site, the GEN added.
Dr. Nolta explained that it was the hypoxic preconditioning that reduced the glucose consumption by the cells, allowing them to survive longer even in a nutrient-deficient environment.
Bioengineered scaffold device and glaucoma drug combo
So, the scientists investigated whether a bioengineered scaffold device that contains hypoxia‐preconditioned allogeneic human MSCs combined with timolol, a drug used to treat glaucoma, can decrease the inflammation in the wounds of diabetic mice and improve healing.
The result shows that the optimized treatment improved the epithelialization - a process where cells repair the wounded area – by 65.6% with the beneficial effects of promoting angiogenesis and decreasing inflammation.
The reason why they added the glaucoma drug to their latest study was that they referenced another study from the UC Davis as well, in which authors demonstrated how wound tissue generates catecholamine, which are hormones that play a significant role in the body’s response to stress by elevated blood glucose levels and blood pressure. In that study, it was found that catecholamine impairs healing and timolol is known to reverse the negative effects of catecholamine.
In their latest study, Dr. Nolta and colleagues gathered MSCs from the bone marrow of healthy human donors on the circular matrix scaffolds. They also tested several MSCs concentrates to determine the optimal MSC dosing. Then, the team incubated the scaffolds in timolol at 1% hypoxia (oxygen) in the MSC culture medium. The next step was to apply the scaffolds to the wounds of a group of diabetic mice. They then have a group of control mice treated with a matrix scaffold only (no timolol or MSCs). The purpose was to see the efficacy of the animal’s cells in reconstructing the damaged tissue compared to wounds treated with timolol and MSC matrix.
Overall, the combination of timolol and MSCs successfully reduced inflammatory response and improved wound healing. The recent UC Davis study also appeared in the journal Stem Cells Translational Medicine.
Diabetes and diabetic foot: statistics
Our World in Data, a scientific online publication that focuses on large global problems, shares the following countries with the highest diabetes prevalence in 2017: New Caledonia (23.36% of population ages 20 to 79), Mauritius (22.02%), Papua New Guinea (17.65%), Saudi Arabia (17.72%), Egypt (17.31%), United Arab Emirates (17.26%), Sudan (15.67%), and Fiji (14.49%).
The lifetime incidence of foot ulcers in diabetic patients is 19-34% but regular foot exams can reduce amputation rates by 45 to 85%, according to the American College of Physicians. But prevention is the best way to treat a diabetic foot. Recommended guidelines include seeing a podiatrist regularly.
The recent findings from the UC Davis study suggest a unique approach that has the potential to provide superior healing responses in people with diabetic wounds.