TY - JOUR
T1 - 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
AU - Rey-Rico, Ana
AU - Venkatesan, Jagadeesh K.
AU - Frisch, Janina
AU - Schmitt, Gertrud
AU - Monge-Marcet, Amália
AU - Lopez-Chicon, Patricia
AU - Mata, Alvaro
AU - Semino, Carlos
AU - Madry, Henning
AU - Cucchiarini, Magali
N1 - Funding Information:
This research was funded by a grant from the Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation , Davos, Switzerland. We thank R. J. Samulski (The Gene Therapy Center, University of North Carolina, Chapel Hill, NC), X. Xiao (The Gene Therapy Center, University of Pittsburgh, Pittsburgh, PA), and E. F. Terwilliger (Division of Experimental Medicine, Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA) for providing the genomic AAV-2 plasmid clones, the pXX2 and pXX6 plasmids, and the 293 cell line.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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 21 days). 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.
AB - 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 21 days). 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.
KW - Differentiation potency
KW - Human MSCs
KW - Self-assembling hydrogels
KW - rAAV gene transfer
UR - http://www.scopus.com/inward/record.url?scp=84927030976&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2015.02.013
DO - 10.1016/j.actbio.2015.02.013
M3 - Article
C2 - 25712390
AN - SCOPUS:84927030976
SN - 1742-7061
VL - 18
SP - 118
EP - 127
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -