Amini-Nik Saeid, Abdullahi Abdikarim, Vinaik Roohi, Yao Ren Jie Robert, Yu Nancy, Datu Andrea, Belo Cassandra, Jeschke Marc G
2Sunnybrook Research Institute, Toronto, Canada.
3Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Aging Dis. 2022 Apr 1;13(2):540-551. doi: 10.14336/AD.2021.1008. eCollection 2022 Apr.
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. , 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.
伤口愈合受损是老年人群中的一个主要问题,与巨大的健康和经济负担相关,且随着老龄化人口的增加呈指数级上升。虽然衰老导致皮肤愈合紊乱的潜在病理生物学与多种遗传和表观遗传因素有关,但对于老年个体伤口愈合过程中的细胞间相互作用,尤其是间充质干细胞(MSC)-巨噬细胞轴,了解甚少。在本研究中,我们使用热损伤动物模型比较成年和幼年小鼠的伤口愈合过程,发现成年动物中MSC数量不足,无法迁移到伤口床,而是局限于伤口边缘。我们确定成年动物伤口中CD90阳性MSC亚群存在缺陷,且该缺陷与F4/80 +巨噬细胞数量呈正相关。此外,我们发现CD90 +细胞优先粘附于形成双细胞的髓样细胞。因此,我们的研究结果表明,在遭受热损伤的成年小鼠中,伤口愈合受损可能是由髓样细胞和间充质细胞之间紊乱的细胞相互作用介导的。