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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5298-5313
Number of pages16
JournalACS Nano
Volume14
Issue number5
DOIs
StatePublished - May 26 2020

Keywords

  • angiogenesis
  • adipose-derived stem cells
  • hyaluronic acid
  • vascular endothelial growth factor
  • muscle
  • liposome

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Leong, J., Hong, Y., Wu, Y., Ko, E., Dvoretskiy, S., Teo, J. Y., Kim, B. S., Kim, K., Jeon, H., Boppart, M., Yang, Y. Y., & Kong, H. (2020). Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair. ACS Nano, 14(5), 5298-5313. https://doi.org/10.1021/acsnano.9b04926