TY - JOUR
T1 - Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair
AU - Hu, Michael S.
AU - Walmsley, Graham G.
AU - Barnes, Leandra A.
AU - Weiskopf, Kipp
AU - Rennert, Robert C.
AU - Duscher, Dominik
AU - Januszyk, Michael
AU - Maan, Zeshaan N.
AU - Hong, Wan Xing
AU - Cheung, Alexander T.M.
AU - Leavitt, Tripp
AU - Marshall, Clement D.
AU - Ransom, Ryan C.
AU - Malhotra, Samir
AU - Moore, Alessandra L.
AU - Rajadas, Jayakumar
AU - Lorenz, H. Peter
AU - Weissman, Irving L.
AU - Gurtner, Geoffrey C.
AU - Longaker, Michael T.
N1 - Funding Information:
The authors thank Reinhold H. Dauskardt for graciously allowing use of a microtester and Mimi Borrelli, Kelly McKenna, and Amira Barkal for their technical assistance. MSH was supported by the California Institute for Regenerative Medicine Clinical Fellow training grant (TG2-01159) and the Stanford University School of Medicine Transplant and Tissue Engineering Fellowship Award. MSH, HPL, and MTL were supported by the American Society of Maxillofacial Surgeons/Maxillofacial Surgeons Foundation Research Grant Award. HPL was supported by NIH grant R01 GM087609 and a gift from Ingrid Lai and Bill Shu in honor of Anthony Shu. HPL, GCG, and MTL were supported by the Hagey Laboratory for Pediatric Regenerative Medicine and The Oak Foundation. ILW was supported by the Ludwig Foundation. ILW and MTL were supported by the Gunn/Olivier Fund. MTL was supported by NIH grant U01 HL099776.
Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85119990513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119990513&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.96260
DO - 10.1172/jci.insight.96260
M3 - Article
C2 - 28978794
AN - SCOPUS:85119990513
SN - 2379-3708
VL - 2
JO - JCI insight
JF - JCI insight
IS - 19
M1 - e96260
ER -
