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.

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.

• Authors: Seppe Vander Beken, Juliane C de Vries, Barbara Meier-Schiesser, Patrick Meyer, Dongsheng Jiang, Anca Sindrilaru, Filipa F Ferreira, Adelheid Hainzl, Susanne Schatz, Jana Muschhammer, Natalie J Scheurmann, Panagiotis Kampilafkos, Andreas M Seitz, Lutz Dürselen, Anita Ignatius, Mark A Kluth, Christoph Ganss, Meinhard Wlaschek, Karmveer Singh, Pallab Maity, Natasha Y Frank, Markus H Frank, Karin Scharffetter-Kochanek
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 37 Issue 8 Pg. 1057-1074 (08 2019) ISSN: 1549-4918 [Electronic] England
• PMID: 31002437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019.

Chemical References

• ABCB5 protein, human
• ABCB5 protein, mouse
• ATP Binding Cassette Transporter, Subfamily B
• IL1RN protein, human
• Il1rn protein, mouse
• Interleukin 1 Receptor Antagonist Protein

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Animals
• Cell Line
• Dermis (metabolism, pathology)
• Disease Models, Animal
• Female
• Humans
• Interleukin 1 Receptor Antagonist Protein (metabolism)
• Iron Overload (metabolism, pathology)
• Leg Ulcer (metabolism, pathology)
• Mesenchymal Stem Cells (metabolism, pathology)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Wound Healing