Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.

Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.
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DOI:
10.1371/journal.pone.0102994
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Xanthoulea S
Xanthoulea S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jetten N;Roumans N;Gijbels MJ;Romano A;Post MJ;de Winther MP;van der Hulst RR;Xanthoulea S

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巨噬细胞在皮肤创伤修复反应的各个阶段都起着至关重要的作用,巨噬细胞功能失调可导致创面修复脱轨。巨噬细胞的表型受创面微环境的影响,在愈合过程中从早期的促炎症(M1)表型演变为修复后期的较少炎性促愈合(M2)表型。本研究的目的是探讨外源性M2巨噬细胞在皮肤损伤小鼠模型中促进创面愈合的可能性。用IL-4或IL-10体外刺激骨髓来源的巨噬细胞,获得两个不同的M2极化细胞亚群,分别为M2a或M2c。将极化的巨噬细胞注射到C57BL/6或糖尿病db/db小鼠的全厚切除皮肤创面中。对照组注射非极化(M0)巨噬细胞或生理盐水。我们的数据表明,尽管M2巨噬细胞在体外表现出抗炎表型,但它们并没有改善野生型小鼠的伤口闭合,而推迟了糖尿病小鼠的愈合。创伤后第15天的创面检查显示M2巨噬细胞处理的糖尿病创面中性粒细胞的再上皮化和持续时间延迟。因此,局部应用体外产生的M2巨噬细胞对皮肤创伤的细胞治疗是不利的,也是禁忌的。
Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.
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