Cells from Diabetic Foot Ulcers Reprogrammed as Stem Cells May Treat Chronic Conditions

Skin cells taken from diabetic foot ulcers can be reprogrammed as pluripotent stem cells and may be used in the future to treat chronic wounds, the results from a pair of recent studies found.

In the first study, published in Cellular Reprogramming, researchers established for the first time that skin cells from diabetic foot ulcers could be reprogrammed to acquire properties of embryonic-like cells.

“The results are encouraging,” said senior author of both studies, Jonathan Garlick, PhD, DDS. “Unlike cells taken from healthy human skin, cells taken from wounds that don’t heal, like diabetic foot ulcers, are difficult to grow and do not restore normal tissue function. By pushing these diabetic wound cells back to this earliest, embryonic stage of development, we have rebooted them to a new starting point to hopefully make them into specific cell types that can heal wounds in patients suffering from non-healing wounds.”

In the first study, researchers were able to successfully reprogram cells from diabetic wounds to an embryonic-like state that turned them into cell types that are imperative for healing wounds.

Researchers used 3 independent criteria to confirm the cells had been reprogrammed to a pluripotent state. Next, 3D engineered tissues were created that previously mimicked numerous features of chronic wounds.

The 3D tissues were used to test the properties of cells from diabetic foot ulcers, revealing that the cells get stuck and form an immature scaffold mostly made up of fibronectin proteins, and are likely to prevent a wound from successfully closing.

“The development of more effective therapies for foot ulcers has been hampered by the lack of realistic wound-healing models that closely mimic the function of the extracellular matrix, which is the scaffold critical for wound repair in skin,” said Anna Maione, PhD, first author of the second study, published in Wound Repair and Regeneration. “This work builds on our paper published in 2015 that showed that cells from diabetic ulcers have fundamental defects which can simulate using our 3D tissue models grown in the lab. These models will be a great way to test new therapeutics that could improve wound healing and prevent limb amputation which can result when treatments fail.”

Fibronectin proteins have been found to be abnormal in other diabetic complications, such as kidney disease. However, this is the first study to directly connect it to the cells taken from diabetic foot ulcers.

“The 3D model is critical because it will allow us to take these studies further,” said Behzad Gerami-Naini, PhD, first author of study in Cellular Reprogramming. “Now that we have confirmed that it’s possible to reprogram wound cells to a very early stage of development we need to study if the can turn into more mature cell types and then study them in our 3D models to see if they will improve healing of chronic wounds.”

Diabetic foot ulcers are a major complication to diabetes, and according to the National Diabetes Statistics Report of 2014, approximately 73,000 non-traumatic lower-limb amputations in 2010 were performed on adults with diabetes who were 20-years-old or older. Furthermore, about 60% of all non-traumatic lower-limb amputations occur in people with diabetes.

“The findings advance commonly held assumptions about how diabetic foot ulcers develop,” Garlick said. “Most importantly, our ability to reprogram these cells gives us new treatment avenues to pursue. The big question is — since we have created induced pluripotent stem cells which we can now make into many cells types important for wound healing – will they be better for wound healing than cells originally taken from the non-healing wound?”