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Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair

Authors
 Jiayu Leong  ;  Yu-Tong Hong  ;  Yu-Fu Wu  ;  Eunkyung Ko  ;  Svyatoslav Dvoretskiy  ;  Jye Yng Teo  ;  Byoung Soo Kim  ;  Kyeongsoo Kim  ;  Hojeong Jeon  ;  Marni Boppart  ;  Yi Yan Yang  ;  Hyunjoon Kong 
Citation
 ACS NANO, Vol.14(5) : 5298-5313, 2020-05 
Journal Title
ACS NANO
ISSN
 1936-0851 
Issue Date
2020-05
MeSH
Adipose Tissue ; Animals ; Cells, Cultured ; Inflammation ; Mice ; Muscles ; Stem Cell Transplantation ; Stem Cells* ; Vascular Endothelial Growth Factor A*
Keywords
angiogenesis ; adipose-derived stem cells ; hyaluronic acid ; vascular endothelial growth factor ; muscle ; liposome
Abstract
Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor alpha (TNF alpha), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNF alpha. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNF alpha carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE(2)) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.
Files in This Item:
T9992020334.pdf Download
DOI
10.1021/acsnano.9b04926
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190112
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