title: Effective and durable genetic modification of human mesenchymal stem cells via controlled release of rAAV vectors from self-assembling peptide hydrogels with a maintained differentiation potency.
abstract: Controlling the release of recombinant adeno-associated virus (rAAV) vectors from biocompatible materials is a novel, attractive approach to increase the residence time and effectiveness of a gene carrier at a defined target site. Self-assembling peptides have an ability to form stable hydrogels and encapsulate cells upon exposure to physiological pH and ionic strength. Here, we examined the capacity of the peptide hydrogel RAD16-I in a pure (RAD) form or combined with hyaluronic acid (RAD-HA) to release rAAV vectors as a means to genetically modify primary human bone marrow-derived mesenchymal stem cells (hMSCs), a potent source of cells for regenerative medicine. Specifically, we demonstrate the ability of the systems to efficiently encapsulate and release rAAV vectors in a sustained, controlled manner for the effective transduction of hMSCs (up to 80%) without deleterious effects on cell viability (up to 100%) or on their potential for chondrogenic differentiation over time (up to 21days). The present study demonstrates that RAD16-I is an advantageous material with tunable properties to control the release of rAAV vectors as a promising tool to develop new, improved therapeutic approaches for tissue engineering in vivo.
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Rey-Rico
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany.
authors.forename: Jagadeesh K
authors.initials: JK
authors.lastname: Venkatesan
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Frisch
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Schmitt
authors.affiliation: Queen Mary University of London, London, United Kingdom.
authors.forename: Amália
authors.initials: A
authors.lastname: Monge-Marcet
authors.affiliation: IQS Universitat Ramon Llull, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lopez-Chicon
authors.affiliation: Queen Mary University of London, London, United Kingdom.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mata
authors.affiliation: IQS Universitat Ramon Llull, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Semino
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Madry
authors.affiliation: Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr, Bldg 37, D-66421 Homburg/Saar, Germany. Electronic address: mmcucchiarini@hotmail.com.
authors.forename: Magali
authors.initials: M
authors.lastname: Cucchiarini
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D003692:Delayed-Action Preparations; D000229:Dependovirus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005821:Genetic Techniques; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D020100:Hydrogels / Q000494:pharmacology*; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D010455:Peptides; C546681:RADA16-I; D006820:Hyaluronic Acid
keywords: Differentiation potency; Human MSCs; Self-assembling hydrogels; rAAV gene transfer