Thermoresponsive Gel Embedded with Adipose Stem-Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy.
Amanda K A SilvaSilvana PerrettaGuillaume PerrodLaetitia PidialVéronique LindnerFlorent CarnShony LemieuxDamien AlloyeauImane BoucennaPhilippe MenaschéBernard DallemagneFlorence GazeauClaire WilhelmChristophe CellierOlivier ClémentGabriel RahmiPublished in: ACS nano (2018)
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.
Keyphrases
- wound healing
- minimally invasive
- adipose tissue
- inflammatory response
- hyaluronic acid
- stem cells
- heart failure
- insulin resistance
- mesenchymal stem cells
- type diabetes
- brain injury
- endothelial cells
- risk assessment
- atrial fibrillation
- lipopolysaccharide induced
- bone marrow
- robot assisted
- anti inflammatory
- subarachnoid hemorrhage
- human health
- lps induced