Diabetic foot ulcers (DFUs) represent a significant complication of diabetes mellitus,
affecting a substantial proportion of patients and often leading to severe morbidity,
prolonged hospital stays, and increased healthcare costs [1]. The management of DFUs
remains a considerable challenge due to their chronic nature and the complex interplay of
factors that impede healing, including poor blood circulation, neuropathy, and infection
and this leads to the increase in the number of amputations [2].
The prevalence of diabetes mellitus (DM) is rising globally, with projections of affected
individuals increasing from 463 million in 2019 to 642 million by 2040 [3], particularly
in regions like the Middle East and North Africa (MENA), where Egypt ranks among the top
10 countries with the highest diabetes prevalence [4].Diabetic foot ulcers (DFUs) are a
common and debilitating complication of DM, with a lifetime risk of 19-34% among diabetic
patients and accounting for 85% of diabetic lower-limb amputations (DLLA) [5, 6].These
ulcers significantly contribute to morbidity, prolonged hospitalizations, and a high
socio-economic burden while being associated with post-amputation mortality rates of
24.6% within 5 years and 45.4% within 10 years [7].
The scale of this challenge demands urgent attention to innovative, cost-effective
interventions to alleviate both human suffering and financial strain[8], various
approaches have been developed to enhance healing and prevent recurrence, such as
advanced wound dressings, offloading techniques, and the use of growth factors or skin
substitutes [9]. But they are still far from ideal. As such, there is an urgent need for
innovative therapeutic strategies that can effectively promote wound healing and improve
patient outcomes. applications.
In recent years, mesenchymal stem cell (MSC) - derived exosomes have garnered attention
in regenerative medicine. Exosomes are small extracellular vesicles that facilitate
intercellular communication by transporting proteins, lipids, and nucleic acids.
MSC-derived exosomes have demonstrated the ability to modulate inflammation, promote
angiogenesis, and enhance tissue repair across various conditions, including
cardiovascular diseases, osteoarthritis, and chronic wounds [10].
Traditionally, bone marrow (BM) has been the primary source of pluripotent MSCs. However,
harvesting BM requires an invasive procedure, and with advancing age, the quantity,
differentiation potential, and lifespan of BM-derived MSCs decline significantly So
alternative sources such as the umbilical cord and adipose tissue (AD) have gained
attention [11] . Among these, umbilical cord-derived MSCs, specifically those from
Wharton's jelly (WJ), known as Wharton's jelly mesenchymal stem cells (WJ-MSCs) have
unique properties. WJ-MSCs are highly accessible, ethically uncontroversial, and offer
significant advantages, including a strong differentiation potential and an
immunoprivileged status. Moreover, they exhibit characteristics similar to embryonic stem
cells including rapid cell division and high expansion capacity[12].
Experimental evidence suggests that WJ-MSCs demonstrate superior proliferation potential
compared other MSC such as adipose tissue-derived MSCs (AD-MSCs). These properties
position WJ-MSCs as an attractive option for regenerative medicine and therapeutic
applications [13, 14].
This study aims to investigate the efficacy and safety of the topical application of
WJ-MSC-derived exosomes in patients with chronic DFUs, thereby exploring a potential new
treatment paradigm for this debilitating condition. The outcomes of this research could
not only enhance healing rates but also significantly improve the quality of life for
individuals suffering from chronic diabetic foot ulcers.
