Newly Defined ATP‐Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron‐Overload Wounds via Secretion of Interleukin‐1 Receptor Antagonist. (13th May 2019)

• Record Type: Journal Article
• Authors: Vander Beken, Seppe; de Vries, Juliane C.; Meier‐Schiesser, Barbara; Meyer, Patrick; Jiang, Dongsheng; Sindrilaru, Anca; Ferreira, Filipa F.; Hainzl, Adelheid; Schatz, Susanne; Muschhammer, Jana; Scheurmann, Natalie J.; Kampilafkos, Panagiotis; Seitz, Andreas M.; Dürselen, Lutz; Ignatius, Anita; Kluth, Mark A.; Ganss, Christoph; Wlaschek, Meinhard; Singh, Karmveer; Maity, Pallab; Frank, Natasha Y.; Frank, Markus H.; Scharffetter‐Kochanek, Karin
• Is Part Of: Stem cells. Volume 37:Number 8(2019)
• Page Start: 1057
• Page End: 1074
• Publication Date: 2019-05-13
• Subjects: Clinical translation -- Cell surface markers -- Mesenchymal stem cells -- Tissue regeneration -- Tissue‐specific stem cells -- Xenotransplantation; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3022
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP‐binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5 + ‐derived mesenchymal stem cells (MSCs) attenuated macrophage‐dominated inflammation and thereby accelerated healing of full‐thickness excisional wounds in the iron‐overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin‐1 receptor antagonist (IL‐1RA) secreted by ABCB5 + ‐derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti‐inflammatory M2 macrophages at the wound site. The beneficial anti‐inflammatory effect of IL‐1RA released from ABCB5 + ‐derived MSCs on human wound macrophages was conserved in humanized NOD‐ scid IL2rγ null mice. In conclusion, human dermal ABCB5 + cells represent a novel, easily accessible, and marker‐enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans.Stem Cells 2019;37:1057–1074 Abstract : In chronic wounds, M1 macrophages and their autocrine amplification of inflammasome‐generated interleukin‐1 (IL‐1) beta perpetuates a proinflammatory environment impeding the progression through normal phases of wound healing. IL‐1 receptor antagonist adaptively secreted by ATP‐binding cassette subfamily B member 5 + mesenchymal stem cells when exposed to the M1 macrophage imprinted proinflammatory wound environment, attenuates this vicious cycle, and leads to a shift from proinflammatory M1 toward anti‐inflammatory, wound healing‐promoting M2 macrophages as observed in normal wound healing.