Skin, the body’s outermost layer, serves as a vital defense against pathogens and is integral to maintaining overall bodily balance. Chronic skin wounds can result from various factors such as trauma, burns, and long-term illnesses like diabetes and peripheral artery disease. These persistent wounds, defined as those that fail to heal within a three-month timeframe, are on the rise due to increasing rates of obesity and diabetes. Individuals with severe skin damage face severe consequences, including potential impairment or even mortality. Consequently, chronic wounds remain a pressing healthcare challenge, exacerbated by a growing patient population and a shortage of effective therapies.
Conventional approaches to managing chronic wounds primarily focus on addressing underlying causes, including infection and restricted blood flow. While typical wound treatments like manual debridement, topical antibiotics, and compression bandages are standard, more advanced therapies such as tissue-engineered skin grafts and growth factors are gaining traction. Despite notable advancements, clinical outcomes remain suboptimal, with over half of chronic wounds resisting current treatment modalities, underscoring the urgent need for improved therapeutic options.
Mesenchymal stem cells (MSCs) have emerged as a promising alternative for addressing a range of challenging tissue injuries and disorders. Their presence within skin tissues and their critical roles in both normal wound healing and skin stability suggest their potential utility in chronic wound healing. MSCs possess a remarkable ability to respond rapidly to biological signals linked to inflammation, tissue damage, and cell death, serving as a reservoir of endogenous cells for tissue repair and regeneration. In various animal models, including those involving diabetic skin ulcers, osteoarthritis, and corneal damage, MSCs have been observed to differentiate into cells that repair damaged tissues. Moreover, they exhibit the capacity to migrate to distant injured sites, facilitating tissue regeneration.
The promising results from animal studies have led to the progression of MSC-based therapy into clinical trials for chronic wound treatment. In particular, clinical trials involving MSC transplantation for lower extremity ulcers have shown encouraging outcomes. Notably, a direct correlation was observed between the density of bone marrow MSCs administered to chronic wounds and the reduction in ulcer size. In other instances, additional sources of MSCs, such as adipose MSCs combined with human acellular collagen matrix, have been employed to create a biological dressing, resulting in significant improvements in skin angiogenesis and wound remodeling following implantation. Phase 1 research involving intramuscular administration of placenta-derived MSCs to diabetic patients with index ulcers reported preliminary indications of ulcer healing three months post-treatment.
In conclusion, MSCs have exhibited significant promise in promoting the healing of chronic wounds through numerous animal experiments. Their multifaceted roles in wound healing, particularly their paracrine effects, are believed to be the primary mechanisms driving restoration. Clinical trials have demonstrated improved wound healing outcomes when MSCs are employed to treat various types of chronic wounds, aligning with the positive findings from preclinical investigations. Current evidence strongly supports MSC-based therapy as a promising and viable treatment option for chronic wounds.
Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ. Mesenchymal stem cells for chronic wound healing: current status of preclinical and clinical studies. Tissue Engineering Part B: Reviews. 2020 Dec 1;26(6):555-70.