Abstract
Introduction Although chronic wounds are a major personal and economic burden, treatment options are still limited. Among those options, adipose-derived stromal cell- (ASC-) based therapies rank as a promising approach but are restricted by the harsh wound environment. Here we use a commercially available fibrin glue to provide a deliverable niche for ASCs in chronic wounds. Material and Methods To investigate the in vitro effect of fibrin glue, cultivation experiments were performed and key cytokines for regeneration were quantified. By using an established murine chronic diabetic wound-healing model, we evaluated the influence of fibrin glue spray seeding on cell survival (In Vivo Imaging System, IVIS), wound healing (wound closure kinetics), and neovascularization of healed wounds (CD31 immunohistochemistry). Results Fibrin glue seeding leads to a significantly enhanced secretion of key cytokines (SDF-1, bFGF, and MMP-2) of human ASCs in vitro. IVIS imaging showed a significantly prolonged murine ASC survival in diabetic wounds and significantly accelerated complete wound closure in the fibrin glue seeded group. CD31 immunohistochemistry revealed significantly more neovascularization in healed wounds treated with ASCs spray seeded in fibrin glue vs. ASC injected into the wound bed. Conclusion Although several vehicles have shown to successfully act as cell carrier systems in preclinical trials, regulatory issues have prohibited clinical usage for chronic wounds. By demonstrating the ability of fibrin glue to act as a carrier vehicle for ASCs, while simultaneously enhancing cellular regenerative function and viability, this study is a proponent of clinical translation for ASC-based therapies.
Highlights
Chronic wounds are a major personal and economic burden, treatment options are still limited
Within the last few years, stem cell therapies have emerged as a promising approach to address nonhealing wounds [3]
adipose-derived stem cells (ASCs) were expanded under standard cell culture conditions in a StemMACS expansion medium (Miltenyi Biotec, Bergisch Gladbach, Germany)
Summary
Chronic wounds are a major personal and economic burden, treatment options are still limited. Chronic wounds represent a major healthcare issue, significantly affecting the quality of life of the individual and placing a substantial economic burden on the society, annually affecting 6.5 million people and costing more than 25 billion dollars in USA alone [1]. This has been accentuated by an increasingly aging population and has directed research towards both efficient prevention and effective treatments of chronic wounds [1].
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