Fibrin Glue Enhances Adipose-Derived Stromal Cell Cytokine Secretion and Survival Conferring Accelerated Diabetic Wound Healing

纤维蛋白胶增强脂肪衍生的基质细胞因子分泌和存活,加速糖尿病伤口愈合

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作者:Ursula Hopfner #, Matthias M Aitzetmueller #, Philipp Neßbach, Michael S Hu, Hans-Guenther Machens, Zeshaan N Maan, Dominik Duscher

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.

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).

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.

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