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Thermoresponsive Gel Embedded with Adipose Stem-Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy
- Source :
- ACS Nano, ACS Nano, American Chemical Society, 2018, 12 (10), pp.9800-9814. ⟨10.1021/acsnano.8b00117⟩, ACS Nano, 2018, 12 (10), pp.9800-9814. ⟨10.1021/acsnano.8b00117⟩
- Publication Year :
- 2018
-
Abstract
- Extracellular vesicles (EVs) are increasingly envisioned as the next generation of biological pro-regenerative nanotherapeutic agents, as has already been demonstrated for heart, kidney, liver, and brain tissues; lung injury repair; and skin regeneration. Herein, we explore another potential EV therapeutic application, fistula healing, together with a local minimally invasive delivery strategy. Allogenic extracellular vesicles (EVs) from adipose tissue-derived stromal cells (ASCs) are administered in a porcine fistula model through a thermoresponsive Pluronic F-127 (PF-127) gel, injected locally at 4 °C and gelling at body temperature to retain EVs in the entire fistula tract. Complete fistula healing is reported to be 100% for the gel plus EVs group, 67% for the gel group, and 0% for the control, supporting the therapeutic use of Pluronic F-127 gel alone or combined with EVs. However, only the combination of gel and EVs results in a statistically significant (i) reduction of fibrosis, (ii) decline of inflammatory response, (iii) decrease in the density of myofibroblasts, and (iv) increase of angiogenesis. Overall, we demonstrate that ASC-EV delivery into a PF-127 gel represents a successful local minimally invasive strategy to induce a therapeutic effect in a swine fistula model. Our study presents prospects for EV administration strategies and for the management of post-operative fistulas.
- Subjects :
- 0301 basic medicine
Angiogenesis
Swine
[SDV]Life Sciences [q-bio]
General Physics and Astronomy
Adipose tissue
Poloxamer
Lung injury
03 medical and health sciences
Esophageal Fistula
Extracellular Vesicles
0302 clinical medicine
Fibrosis
medicine
Animals
General Materials Science
ComputingMilieux_MISCELLANEOUS
[PHYS]Physics [physics]
Inflammation
Wound Healing
Chemistry
Regeneration (biology)
Stem Cells
Mesenchymal stem cell
General Engineering
Temperature
medicine.disease
030104 developmental biology
Adipose Tissue
030220 oncology & carcinogenesis
Cancer research
Stem cell
Gels
Subjects
Details
- ISSN :
- 1936086X and 19360851
- Volume :
- 12
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- ACS nano
- Accession number :
- edsair.doi.dedup.....ac8edf7951dd7a8e5bc23ac5a5484b68