Marrow-Derived Stromal Cell Delivery on Fibrin Microbeads Can Correct Radiation-Induced Wound-Healing Deficits

Abstract

Skin that is exposed to radiation has an impaired ability to heal wounds. This is especially true for whole body irradiation, where even moderate non-lethal doses can result in wound healing deficits. Our previous attempts to administer dermal cells locally to wounds to correct radiation-induced deficits were hampered by poor cell retention. Here we improve the outcome by using biodegradable fibrin microbeads (FMB) to isolate a population of mesenchymal marrow-derived stromal cells (MSC) from murine bone marrow by their specific binding to the fibrin matrix, culture them to high density in vitro and deliver them as MSC on FMB at the wound site. MSC are retained and proliferate locally and assist wounds gain tensile strength in whole body irradiated mice with or without additional skin only exposure. MSC-FMB were effective in 2 different mouse strains but were ineffective across a major histocompatability barrier. Remarkably, irradiated mice whose wounds were treated with MSC-FMB showed enhanced hair regrowth suggesting indirect effect on the correction of radiation-induced follicular damage. Further studies showed that additional wound healing benefit could be gained by administration of G-CSF and AMD3100. Collagen strips coated with haptides and MSCs were also highly effective in correcting radiation-induced wound healing deficits.