Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, and.
Institute for Stem Cell Biology and Regenerative Medicine and Ludwig Center, Stanford University School of Medicine, Stanford, California, USA.
JCI Insight. 2017 Oct 5;2(19):96260. doi: 10.1172/jci.insight.96260.
The monocyte lineage is essential to normal wound healing. Macrophage inhibition or knockout in mice results in impaired wound healing through reduced neovascularization, granulation tissue formation, and reepithelialization. Numerous studies have either depleted macrophages or reduced their activity in the context of wound healing. Here, we demonstrate that by increasing the number of macrophages or monocytes in the wound site above physiologic levels via pullulan-collagen composite dermal hydrogel scaffold delivery, the rate of wound healing can be significantly accelerated in both wild-type and diabetic mice, with no adverse effect on the quality of repair. Macrophages transplanted onto wounds differentiate into M1 and M2 phenotypes of different proportions at various time points, ultimately increasing angiogenesis. Given that monocytes can be readily isolated from peripheral blood without in vitro manipulation, these findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases.
单核细胞谱系对于正常的伤口愈合至关重要。在小鼠中,巨噬细胞的抑制或敲除会导致新生血管形成、肉芽组织形成和上皮再形成减少,从而导致伤口愈合受损。许多研究已经在伤口愈合的背景下耗尽了巨噬细胞或降低了它们的活性。在这里,我们证明,通过增加伤口部位的巨噬细胞或单核细胞数量,使其高于生理水平,使用普鲁兰-胶原复合真皮水凝胶支架递送,可以显著加速野生型和糖尿病小鼠的伤口愈合速度,而对修复质量没有不良影响。移植到伤口上的巨噬细胞在不同时间点分化为不同比例的 M1 和 M2 表型,最终增加血管生成。鉴于单核细胞可以很容易地从外周血中分离出来,而无需体外操作,这些发现为旨在加速广泛疾病范围内伤口愈合的转化医学提供了希望。