Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair
Michael S. Hu, … , Geoffrey C. Gurtner, Michael T. Longaker
Michael S. Hu, … , Geoffrey C. Gurtner, Michael T. Longaker
Published October 5, 2017
Citation Information: JCI Insight. 2017;2(19):e96260. https://doi.org/10.1172/jci.insight.96260.
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Research Article Therapeutics

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Abstract

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.

Authors

Michael S. Hu, Graham G. Walmsley, Leandra A. Barnes, Kipp Weiskopf, Robert C. Rennert, Dominik Duscher, Michael Januszyk, Zeshaan N. Maan, Wan Xing Hong, Alexander T.M. Cheung, Tripp Leavitt, Clement D. Marshall, Ryan C. Ransom, Samir Malhotra, Alessandra L. Moore, Jayakumar Rajadas, H. Peter Lorenz, Irving L. Weissman, Geoffrey C. Gurtner, Michael T. Longaker

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Figure 1

Macrophage transplantation improves cutaneous wound repair in a humanized model of excisional wound healing in wild-type mice.

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Macrophage transplantation improves cutaneous wound repair in a humanize...
(A) Gross photographs of wounds (n = 10 per group) during healing with macrophage-seeded hydrogel (top row) or with hydrogel control (bottom row). (B) Wound healing curve showing wound size as a percentage of original wound versus time in days (*P < 0.01; 2-tailed unpaired Student’s t test; n = 10 per group). (C) Bar graph showing the difference in time to complete healing between macrophage-treated and control wounds in wild-type mice (*P < 0.001; 2-tailed unpaired Student’s t test; n = 10 per group). (D) CD31 immunofluorescence of fully healed wounds treated with macrophage-seeded hydrogel (top left) versus hydrogel control (top right) and bar graph with immunofluorescence quantification (bottom; *P < 0.05; 2-tailed unpaired Student’s t test; n = 3 per group). Scale bar: 100 μm. (E) Bar graph of tensile strength in fully healed wounds treated with macrophage-seeded hydrogel versus hydrogel control (P > 0.05; 2-tailed unpaired Student’s t test; n = 3 per group). (F) Bar graph of scar size as a percentage of original wound in fully healed wounds treated with macrophage-seeded hydrogel versus hydrogel control (P > 0.05; 2-tailed unpaired Student’s t test; n = 10 per group). (G) Bar graph of scar size as depth ratio to normal unwounded skin, as seen in histology of fully healed wounds treated with macrophage-seeded hydrogel versus hydrogel control (P > 0.05; 2-tailed unpaired Student’s t test; n = 10 per group). (H) Masson’s trichrome stain of fully healed wounds treated with macrophage-seeded hydrogel (left) versus hydrogel control (right). Scale bar: 500 μm.