TY - JOUR
T1 - Improvement of osteogenesis in dental pulp pluripotent-like stem cells by oligopeptide-modified poly(β-amino ester)s
AU - Núñez-Toldrà, Raquel
AU - Dosta, Pere
AU - Montori, Sheyla
AU - Ramos, Víctor
AU - Atari, Maher
AU - Borrós, Salvador
N1 - Funding Information:
This work was partially funded by the Universitat International de Catalunya (UIC Barcelona) and Grup d’Enginyeria dels Materials (GEMAT). UIC would like to acknowledge Agència de Gestió d’ajuts Universitaris i de Recerca, Generalitat de Catalunya (SGR 2014) n° 1060. GEMAT would like to acknowledge Agència de Gestió d’ajuts Universitaris i de Recerca, Generalitat de Catalunya (SGR 2014) n° 1461. The research was also funded through the Grant SAF2012-39947-C02-02 from de Spanish Ministerio de Economia y Competitividad The author R. Núñez-Toldrà was funded by the predoctoral grant Junior Faculty awarded by the Obra Social La Caixa and the UIC. The author Pere Dosta wishes to acknowledge the financial support received from AGAUR (Generalitat de Catalunya) 2016FI_B1 00211. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Funding Information:
This work was partially funded by the Universitat International de Catalunya (UIC Barcelona) and Grup d'Enginyeria dels Materials (GEMAT). UIC would like to acknowledge Ag?ncia de Gesti? d'ajuts Universitaris i de Recerca, Generalitat de Catalunya (SGR 2014) n? 1060. GEMAT would like to acknowledge Ag?ncia de Gesti? d'ajuts Universitaris i de Recerca, Generalitat de Catalunya (SGR 2014) n? 1461. The research was also funded through the Grant SAF2012-39947-C02-02 from de Spanish Ministerio de Economia y Competitividad The author R. N??ez-Toldr? was funded by the predoctoral grant Junior Faculty awarded by the Obra Social La Caixa and the UIC. The author Pere Dosta wishes to acknowledge the financial support received from AGAUR (Generalitat de Catalunya) 2016FI_B1 00211. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Publisher Copyright:
© 2017 Acta Materialia Inc.
PY - 2017/4/15
Y1 - 2017/4/15
N2 - Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. Recently, a new family of poly(β-amino ester)s (pBAEs) with oligopeptide-modified termini showing high transfection efficiency of both siRNA and DNA plasmid has been developed. In this study, oligopeptide-modified pBAEs were used to simultaneously deliver anti-OCT3/4 siRNA, anti-NANOG siRNA, and RUNX2 plasmid to cells from the dental pulp with pluripotent-like characteristics (DPPSC) in order to promote their osteogenic differentiation. Results indicate that transient inhibition of the pluripotency marker OCT3/4 and the overexpression of RUNX2 at day 7 of differentiation markedly increased and accelerated the expression of osteogenic markers. Furthermore, terminally-differentiated cells exhibited higher matrix mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicate that this co-delivery system has high chromosomal stability and minimal cytotoxicity. Therefore, we conclude that such co-delivery strategy is a safe and a quick option for the improvement of DPPSC osteogenic differentiation. Statement of Significance Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. In this study, we propose the use of a new family of oligopeptide-modified pBAEs developed in our group to control the differentiation of dental pulp pluripotential stem cells (DPPSC). In order to promote their osteogenic differentiation. The strategy proposed markedly increased and accelerated the expression of osteogenic markers, cell mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicated that this co-delivery system has high chromosomal stability and minimal cytotoxicity. These findings open a new interesting path in the usage of non-viral gene delivery systems for the control of pluripotential stem cell differentiation.
AB - Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. Recently, a new family of poly(β-amino ester)s (pBAEs) with oligopeptide-modified termini showing high transfection efficiency of both siRNA and DNA plasmid has been developed. In this study, oligopeptide-modified pBAEs were used to simultaneously deliver anti-OCT3/4 siRNA, anti-NANOG siRNA, and RUNX2 plasmid to cells from the dental pulp with pluripotent-like characteristics (DPPSC) in order to promote their osteogenic differentiation. Results indicate that transient inhibition of the pluripotency marker OCT3/4 and the overexpression of RUNX2 at day 7 of differentiation markedly increased and accelerated the expression of osteogenic markers. Furthermore, terminally-differentiated cells exhibited higher matrix mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicate that this co-delivery system has high chromosomal stability and minimal cytotoxicity. Therefore, we conclude that such co-delivery strategy is a safe and a quick option for the improvement of DPPSC osteogenic differentiation. Statement of Significance Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. In this study, we propose the use of a new family of oligopeptide-modified pBAEs developed in our group to control the differentiation of dental pulp pluripotential stem cells (DPPSC). In order to promote their osteogenic differentiation. The strategy proposed markedly increased and accelerated the expression of osteogenic markers, cell mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicated that this co-delivery system has high chromosomal stability and minimal cytotoxicity. These findings open a new interesting path in the usage of non-viral gene delivery systems for the control of pluripotential stem cell differentiation.
KW - DPPSC
KW - Dental pulp
KW - Genetic stability
KW - Non-viral systems
KW - Osteogenic differentiation
KW - Pluripotency
KW - Poly(β-amino ester)
UR - http://www.scopus.com/inward/record.url?scp=85012919456&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000401679100013&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.actbio.2017.01.077
DO - 10.1016/j.actbio.2017.01.077
M3 - Article
C2 - 28159719
AN - SCOPUS:85012919456
SN - 1742-7061
VL - 53
SP - 152
EP - 164
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -