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

• DOI: 10.1016/j.actbio.2015.02.013
• Publication Date: 2015-02-21T16:33:29Z
• Authors: Ana Rey-Rico; Jagadeesh K. Venk...; Janina Frisch; Gertrud Schmitt; Amália Monge-Marcet; Patricia Lopez-Ch...; Alvaro Mata; Carlos Semino; Henning Madry; Magali Cucchiarini
• Keywords: 0301 basic medicine; Cell Survival; Self-assembling hydrogels; Genetic Vectors; Cell Differentiation; Hydrogels; Mesenchymal Stem Cells; Dependovirus; Real-Time Polymerase Chain Reaction; Immunohistochemistry; 3. Good health; Human MSCs; 03 medical and health sciences; Gene Expression Regulation; Genetic Techniques; Delayed-Action Preparations; Humans; Differentiation potency; Hyaluronic Acid; Peptides; rAAV gene transfer; Chondrogenesis

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.