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.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Rey-Rico A,Venkatesan JK,Frisch J,Schmitt G,Monge-Marcet A,Lopez-Chicon P,Mata A,Semino C,Madry H,Cucchiarini M

doi

10.1016/j.actbio.2015.02.013

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

118-27

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(15)00076-8

journal_volume

18

pub_type

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