Researchers recently established that skin cells from diabetic foot ulcers can be reprogrammed to acquire properties of embryonic-like stem cells. The induced pluripotent stem cells could eventually be used to treat chronic wounds. Study results are published online ahead of print in Cellular Reprogramming.
“The results are encouraging. Unlike cells taken from healthy human skin, cells taken from wounds that do not heal — like diabetic foot ulcers — are difficult to grow and do not restore tissue function,” Jonathan Garlick, PhD, DDS, stem cell researcher at Tufts University School of Dental Medicine in Boston, said in a university release. Garlick is lead author of the study in Cellular Reprogramming and of second study that connected the protein fibronectin to a breakdown in the wound-healing process of cells from diabetic foot ulcers.
“By pushing these diabetic wound cells back to its earliest embryonic stages 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,” he said.
Garlick and colleagues successfully reprogrammed diabetic wound cells to an embryonic-like state, then turned them into cell types that aid in wound healing. In a pluripotent state, the cells can turn into a variety of different cell types, including those that can stimulate wound repair.
Next, they created 3-D engineered tissues that mimic the features of chronic wounds. Using these tissues, they tested the properties of cells from diabetic foot ulcers and found cells from diabetic foot ulcers get stuck creating an immature scaffold of fibronectin. This is likely to prevent proper wound closure, according to the release.
“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,” Anna Maione, PhD, first author of the protein fibronectin study, said. “This work builds on our paper published in 2015 that showed that cells from diabetic ulcers have fundamental defects which we can simulate using our 3-D 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.”
Garlick added, “These findings advance commonly-held assumptions about how diabetic foot ulcers develop. Most importantly, our ability to reprogram these cells gives us new treatment avenues to pursue.”
Researchers need to determine whether the pluripotent stem cells are better for wound healing than cells originally taken from the non-healing wound, he said.
Garlick JA, et al. Cell Reprogram. 2016;doi:10.1089/cell.2015.0087.
Garlick JA, et al. Wound Repair Regen. [published online ahead of print April 22, 2016];doi:10.111/wrr.12437.
Disclosure: Please see the full studies for a list of all authors’ relevant financial disclosures.