TY - JOUR
T1 - Protective and healing effects of apoptotic mimic-induced M2-like macrophage polarization on pressure ulcers in young and middle-aged mice
AU - Toita, Riki
AU - Shimizu, Eiko
AU - Murata, Masaharu
AU - Kang, Jeong Hun
N1 - Funding Information:
This work was supported by Kowa Life Science Foundation [no grant number provided]; AMED [grant number JP20fk0210044 ]; and JSPS KAKENHI [grant numbers JP18K12091 , JP17K01386 ]. We would like to thank Editage ( www.editage.com ) for English language editing.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2/10
Y1 - 2021/2/10
N2 - Pressure ulcers (PUs) have no cure and are of significant health and economic concern worldwide, owing to the increasing population of elderly individuals at high risk for PU and who have impaired tissue repair. Macrophages play a pivotal role in PU development and healing. Imbalances between M1 (inflammatory) and M2 (anti-inflammatory/reparative) macrophages result in delayed resolution of inflammation and wound healing. We hypothesized that M1-to-M2 macrophage polarization mediated by artificial apoptotic cell mimics, phosphatidylserine-containing liposomes (PSLs), would protect against PU formation and accelerate PU healing in young (2-month-old) and middle-aged (12-month-old) mice. We used a clinically relevant murine model of ischemia-reperfusion-induced PU. Middle-aged mice displayed the delayed wound healing associated with increased inflammation, decreased collagen deposition, reduced angiogenesis, and delayed wound closure relative to their younger counterparts. PSL treatment significantly inhibited PU formation and promoted tissue remodeling in both age groups. These effects were mediated by increased M1-to-M2 macrophage polarization, induced by the PSLs. Thus, this study suggests, for the first time, that PSL-induced M2-like macrophage polarization is a promising strategy to protect against PU formation and promote PU repair in human patients of all ages.
AB - Pressure ulcers (PUs) have no cure and are of significant health and economic concern worldwide, owing to the increasing population of elderly individuals at high risk for PU and who have impaired tissue repair. Macrophages play a pivotal role in PU development and healing. Imbalances between M1 (inflammatory) and M2 (anti-inflammatory/reparative) macrophages result in delayed resolution of inflammation and wound healing. We hypothesized that M1-to-M2 macrophage polarization mediated by artificial apoptotic cell mimics, phosphatidylserine-containing liposomes (PSLs), would protect against PU formation and accelerate PU healing in young (2-month-old) and middle-aged (12-month-old) mice. We used a clinically relevant murine model of ischemia-reperfusion-induced PU. Middle-aged mice displayed the delayed wound healing associated with increased inflammation, decreased collagen deposition, reduced angiogenesis, and delayed wound closure relative to their younger counterparts. PSL treatment significantly inhibited PU formation and promoted tissue remodeling in both age groups. These effects were mediated by increased M1-to-M2 macrophage polarization, induced by the PSLs. Thus, this study suggests, for the first time, that PSL-induced M2-like macrophage polarization is a promising strategy to protect against PU formation and promote PU repair in human patients of all ages.
UR - http://www.scopus.com/inward/record.url?scp=85099248194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099248194&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.12.052
DO - 10.1016/j.jconrel.2020.12.052
M3 - Article
C2 - 33388342
AN - SCOPUS:85099248194
VL - 330
SP - 705
EP - 714
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -