PEO-PPO-PEO micelles as effective rAAV-mediated gene delivery systems to target human mesenchymal stem cells without altering their differentiation potency

Acta Biomaterialia
Ana Rey-RicoMagali Cucchiarini

Abstract

Recombinant adeno-associated viral (rAAV) vectors are clinically adapted gene transfer vectors for direct human cartilage regenerative medicine. Their appropriate use in patients is still limited by a relatively low efficacy of vector penetration inside the cells, by the pre-existing humoral immune responses against the viral capsid proteins in a large part of the human population, and by possible inhibition of viral uptake by clinical compounds such as heparin. The delivery of rAAV vectors to their targets using optimized vehicles is therefore under active investigation. Here, we evaluated the possibility of providing rAAV to human bone marrow-derived mesenchymal stem cells (hMSCs), a potent source of cartilage regenerative cells, via self-assembled poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymers as linear poloxamers or X-shaped poloxamines. Encapsulation in poloxamer PF68 and poloxamine T908 polymeric micelles allowed for an effective, durable, and safe modification of hMSCs via rAAV to levels similar to or even higher than those noted upon direct vector application. The copolymers were capable of restoring the transduction of hMSCs with rAAV in conditions of gene transfer inhibition, i.e. in th...Continue Reading

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Citations

Nov 26, 2015·Expert Opinion on Biological Therapy·Henning Madry, Magali Cucchiarini
Oct 17, 2015·Acta Biomaterialia·Ana Rey-Rico, Magali Cucchiarini
Jun 9, 2016·Stem Cells and Development·Janina Frisch, Magali Cucchiarini
Sep 20, 2016·BioMed Research International·Ana Rey-RicoMagali Cucchiarini
Mar 9, 2018·International Journal of Molecular Sciences·Ana Rey-Rico, Magali Cucchiarini
May 5, 2018·Journal of Biomedical Materials Research. Part a·Oliwia JeznachPawe Sajkiewicz
Apr 5, 2017·Bio-medical Materials and Engineering·Magali Cucchiarini
Dec 6, 2018·Nature Reviews. Rheumatology·Magali Cucchiarini, Henning Madry
Aug 6, 2020·International Journal of Molecular Sciences·Dawid SzwedowskiJacek Kruczyński
Dec 15, 2019·Pharmaceutics·Eleonora Russo, Carla Villa
Apr 15, 2020·Pharmaceutics·Fernando Alvarez-RiveraCarmen Alvarez-Lorenzo
Aug 14, 2020·Stem Cells Translational Medicine·Kai SunBing Wang
Aug 16, 2019·Tissue Engineering and Regenerative Medicine·Jagadeesh Kumar VenkatesanMagali Cucchiarini
Feb 9, 2017·Tissue Engineering. Part B, Reviews·Justin L MadrigalEduardo A Silva
Apr 10, 2019·Polymers·Ana Rey-Rico, Magali Cucchiarini
Oct 8, 2020·Biomaterials Science·Kübra Kaygisiz, Christopher V Synatschke
Oct 3, 2020·Pharmaceutics·Henning MadryMagali Cucchiarini
Oct 20, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Maria Aurora GrimaudoCarmen Alvarez-Lorenzo
Jan 10, 2018·ACS Applied Materials & Interfaces·Carlos A García-GonzálezFernando J Monteiro
Aug 29, 2021·International Journal of Pharmaceutics·Ayesha YounasNan Zhang

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