nn8b00117_si_003.pdf (2.56 MB)
Download fileThermoresponsive Gel Embedded with Adipose Stem-Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy
journal contribution
posted on 2018-09-19, 00:00 authored by Amanda K. A. Silva, Silvana Perretta, Guillaume Perrod, Laetitia Pidial, Véronique Lindner, Florent Carn, Shony Lemieux, Damien Alloyeau, Imane Boucenna, Philippe Menasché, Bernard Dallemagne, Florence Gazeau, Claire Wilhelm, Christophe Cellier, Olivier Clément, Gabriel RahmiExtracellular 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.
History
Usage metrics
Categories
Keywords
Thermo-Actuated Delivery Strategy Extracellular vesiclesswine fistula modelEV administration strategiesfistula tractASC-EV deliverybrain tissuesporcine fistula modelbody temperaturepro-regenerative nanotherapeutic agentsPF -127 gelThermoresponsive GelComplete fistula healingdelivery strategygel groupEVs resultsskin regenerationEVs groupPluronic F -127 gelAdipose Stem-Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healingthermoresponsive Pluronic F -127lung injury repairadipose tissue-derived stromal cellsfistula healingAllogenic extracellular vesicles