Content area
Full Text
Background
Diabetes mellitus is a serious metabolic disease characterized by chronic hyperglycemia, with its global incidence steadily increasing. The global prevalence of diabetes is expected to reach 9.8% by 2050, affecting 1.31 billion people [1]. Among the various complications of diabetes, diabetic foot ulcers (DFUs), skin lesions on the feet that often involve the epidermis and dermis and are associated with peripheral neuropathy (PN) and/or peripheral artery disease (PAD), are particularly common, with a lifetime prevalence of 34% [2]. DFUs are also the leading cause of nontraumatic amputations owing to poor wound healing [3, 4]. Current clinical treatments for diabetic wounds primarily involve traditional methods such as debridement surgery, offloading, blood glucose management, infection control, revascularization, and conventional wound care [3]. Although new treatment modalities have emerged in recent years, their therapeutic outcomes remain unsatisfactory [5].
Research studies indicate that reduced neovascularization is a major factor contributing to the delayed healing of diabetic wounds [6, 7]. Vascular endothelial cells are essential for blood vessel formation [8], however, the hyperglycemic environment in patients with diabetes can lead to endothelial cells dysfunction. This dysfunction is driven by the formation of advanced glycation end products (AGEs), increased oxidative stress (OS) and reactive oxygen species (ROS), mitochondrial dysfunction, and activation of the polyol and hexosamine pathways, all of which disrupt angiogenic homeostasis and hinder normal wound healing [9]. Endothelial progenitor cells (EPCs) are typically mobilized and recruited to damaged ischemic tissues by local chemokines. Through processes of proliferation, migration, and differentiation, EPCs mature into endothelial cells and produce pro-angiogenic factors via paracrine signaling, contributing to the repair and maintenance of endothelial cells functions [10]. However, in the hyperglycemic conditions associated with diabetes, the proliferation, migration, differentiation, adhesion, and angiogenic capacity of EPCs are compromised, impairing vascularization at the damaged ischemic sites and leading to chronic, nonhealing wounds [9, 11]. Thus, enhancing neovascularization is critical for effective treatment of diabetic wounds.
Adipose-derived stem cells (ADSCs) have shown significant potential in regenerative medicine and tissue engineering owing to their ability to promote tissue repair and regeneration [12]. Notably, ADSCs have been demonstrated to promote angiogenesis and facilitate neovascularization, both of which are essential for tissue repair and regeneration [7, 13, 14]. Numerous studies have highlighted the positive effects of ADSCs in...