title: 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 nonlethal 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 (FMBs) to isolate a population of mesenchymal marrow-derived stromal cells (MSCs) from murine bone marrow by their specific binding to the fibrin matrix, culture them to high density in vitro, and deliver them as MSCs on FMBs at the wound site. MSCs are retained locally, proliferate in site, and assist wounds in gaining tensile strength in whole-body irradiated mice with or without additional skin-only exposure. MSC-FMBs were effective in two different mouse strains but were ineffective across a major histocompatability barrier. Remarkably, irradiated mice whose wounds were treated with MSC-FMBs 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 granulocyte colony-stimulating factor and AMD3100. Collagen strips coated with haptides and MSCs were also highly effective in correcting radiation-induced wound-healing deficits.
authors.affiliation: Department Radiation Oncology, David Geffen School Medicine, University of California, Los Angeles, Los Angeles, California 90095-1714, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Xie
authors.forename: Raphael
authors.initials: R
authors.lastname: Gorodetsky
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Micewicz
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Micevicz
authors.forename: Natalia C
authors.initials: NC
authors.lastname: Mackenzie
authors.forename: Elena
authors.initials: E
authors.lastname: Gaberman
authors.forename: Lilia
authors.initials: L
authors.lastname: Levdansky
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002478:Cells, Cultured; D020405:Dermis / Q000502:physiology / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D005337:Fibrin / Q000494:pharmacology* / Q000502:physiology; D005856:Germ-Free Life; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008863:Microspheres; D011833:Radiation Injuries, Experimental / Q000503:physiopathology / Q000628:therapy*; D012871:Skin Diseases / Q000503:physiopathology / Q000628:therapy*; D013718:Tensile Strength / Q000502:physiology; D014916:Whole-Body Irradiation / Q000009:adverse effects; D014945:Wound Healing / Q000502:physiology* / Q000528:radiation effects
chemical_list: D005337:Fibrin