Aging Impairs the Cellular Interplay between Myeloid Cells and Mesenchymal Cells during Skin Healing in Mice.
Aging Impairs the Cellular Interplay between Myeloid Cells and Mesenchymal Cells during Skin Healing in Mice.
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DOI：
10.14336/ad.2021.1008
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发表时间：
2022-04
影响因子：
7.4
通讯作者：
Jeschke MG
中科院分区：
文献类型：
--
作者：
Amini-Nik S;Abdullahi A;Vinaik R;Yao RJR;Yu N;Datu A;Belo C;Jeschke MG
伤口愈合受损是老年人口中的一个主要问题，与巨大的健康和经济负担有关，随着人口老龄化的加剧，这一负担呈指数级增长。虽然衰老引起皮肤愈合紊乱的潜在病理生物学与几种遗传和表观遗传因素有关，但对老年人伤口愈合过程中细胞间相互作用知之甚少，特别是间充质干细胞(MSCs)-巨噬细胞轴。在本研究中，我们通过热损伤动物模型，比较了成年小鼠和幼鼠的伤口愈合过程，我们发现成年动物中不足的MSCs池缺乏向伤口床的迁移，而是局限于伤口边缘。我们发现在成年动物的伤口中缺乏cd90阳性的MSC亚群，这与F4/80+巨噬细胞的数量呈正相关。在体外，我们发现CD90+细胞优先粘附于髓细胞形成双线细胞。因此，我们的研究结果强调，在遭受热损伤的成年小鼠中，伤口愈合受损可能是由髓细胞和间充质细胞之间的细胞相互作用受到干扰所介导的。
Impaired wound healing is a major issue in the elderly population and is associated with substantial health and economic burden, which is exponentially increasing with the growing aging population. While the underlying pathobiology of disturbed skin healing by aging is linked to several genetic and epigenetic factors, little is known about the cell-cell interaction during the wound healing process in aged individuals, particularly the mesenchymal stem cell (MSCs)-macrophages axis. In this study, by using a thermal injury animal model in which we compared the wound healing process of adult and young mice, we found that the insufficient pool of MSCs in adult animals are deficient in migrating to the wound bed and instead are restricted to the wound edge. We identified a deficiency of a CD90-positive MSC subpopulation in the wounds of adult animals, which is positively correlated with the number of F4/80+ macrophages. In vitro, we found that CD90+ cells preferentially adhere to the myeloid cells forming doublet cells. Thus, our findings highlight that in adult mice subjected to a thermal injury, impaired wound healing is likely mediated by a disturbed cellular interplay between myeloid cells and mesenchymal cells.