@article{32c5a465f80540dab657b58744ba8971,
title = "Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair",
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 α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE2) 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.",
keywords = "angiogenesis, adipose-derived stem cells, hyaluronic acid, vascular endothelial growth factor, muscle, liposome",
author = "Jiayu Leong and Yu-tong Hong and Yu-fu Wu and Eunkyung Ko and Svyatoslav Dvoretskiy and Teo, {Jye Yng} and Kim, {Byoung Soo} and Kyeongsoo Kim and Hojeong Jeon and Marni Boppart and Yang, {Yi Yan} and Hyunjoon Kong",
note = "Funding Information: Dynamic light scattering was carried out in part in the Fredrick Seitz Materials Research Laboratory Central Facilities, University of Illinois. J.L. and J.Y.T. gratefully acknowledge the A*STAR Graduate Scholarship (Overseas) from the Agency for Science, Technology and Research (A*STAR) Singapore. Y.Y.Y. is grateful for the support from the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, A*STAR, Singapore). Research reported in this publication was supported by the Korea Institute of Science and Technology (2E29340 to H.J.), National Institutes of Health (1R21 HL131469 to H.K. and M.B.), and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under (T32EB019944 to E.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: ynamic light scattering was carried out in part in the Fredrick Seitz Materials Research Laboratory Central Facilities University of Illinois. J.L. and J.Y.T. gratefully acknowledge the ASTAR Graduate Scholarship (Overseas) from the Agency for Science Technology and Research (ASTAR) Singapore. Y.Y.Y. is grateful for the support from the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, A*STAR, Singapore). Research reported in this publication was supported by the Korea Institute of Science and Technology (2E29340 to H.J.), National Institutes of Health (1R21 HL131469 to H.K. and M.B.), and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under (T32EB019944 to E.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = may,
day = "26",
doi = "10.1021/acsnano.9b04926",
language = "English (US)",
volume = "14",
pages = "5298--5313",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "5",
}