title: Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation of mesenchymal stem cells.
abstract: Noggin is a specific antagonist of bone morphogenetic proteins (BMPs) that can prevent the interaction of BMPs with their receptors. RNA interfering molecules have been used to downregulate noggin expression and thereby stimulate BMP signaling and osteogenesis. Cationic liposomes are considered one of the most efficient non-viral systems for gene delivery. In the past decade, non-phospholipid liposomes (Sterosomes) formulated with single-chain amphiphiles and high content of sterols have been developed. In particular, Sterosomes composed of stearylamine (SA) and cholesterol (Chol) display distinct properties compared with traditional phospholipid liposomes, including increased positive surface charges and enhanced particle stability. Herein, we report SA/Chol Sterosome and small interfering RNA (siRNA) complexes that significantly enhanced cellular uptake and gene knockdown efficiencies in adipose derived mesenchymal stem cells with minimal cytotoxicity compared with commercially available lipofectamine 2000. Furthermore, we confirmed osteogenic efficacy of these Sterosomes loaded with noggin siRNA in in vitro two- and three-dimensional settings as well as in a mouse calvarial defect model. The delivery of siRNA via novel SA/Chol Sterosomes presents a powerful method for efficient gene knockdown. These distinct nanoparticles may present a promising alternative approach for gene delivery.
authors: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
authors: Zhong-Kai
authors: ZK
authors: Cui
authors: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
authors: Jiabing
authors: J
authors: Fan
authors: Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States.
authors: Soyon
authors: S
authors: Kim
authors: Division of Diagnostic and Surgical Sciences, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
authors: Olga
authors: O
authors: Bezouglaia
authors: Division of Diagnostic and Surgical Sciences, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
authors: Armita
authors: A
authors: Fartash
authors: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States.
authors: Benjamin M
authors: BM
authors: Wu
authors: Division of Diagnostic and Surgical Sciences, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
authors: Tara
authors: T
authors: Aghaloo
authors: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States. Electronic address: leemin@ucla.edu.
authors: Min
authors: M
authors: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000588:Amines / Q000737:chemistry; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D020100:Hydrogels / Q000737:chemistry; D008081:Liposomes; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity; D010012:Osteogenesis; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D011859:Radiography; D012886:Skull / Q000000981:diagnostic imaging / Q000293:injuries; D000099176:Noggin Protein
chemical_list: D000588:Amines; D002352:Carrier Proteins; D048271:Chitosan; D002784:Cholesterol; D020100:Hydrogels; D008081:Liposomes; D034741:RNA, Small Interfering; D000099176:Noggin Protein; C009317:stearylamine
keywords: Cholesterol; Mesenchymal stem cells; Osteogenic differentiation; Stearylamine; Sterosomes; siRNA