title: Enhanced survival of transplanted human adipose-derived stem cells by co-delivery with liposomal apoptosome inhibitor in fibrin gel matrix.
abstract: To improve the survival of transplanted human adipose-derived stem cells (ADSCs), a liposome preparation containing the apoptosome inhibitor, NS3694, was formulated and co-delivered with ADSCs in fibrin gel scaffolds. Liposomes provided enhanced effect on ADSC proliferation in vitro as compared to free drug. Exposure of ADSCs to liposomal NS3694 for 7 days did not affect the surface marker expression profile. NS3694 encapsulated in negatively charged liposomes composed of phosphatidylcholine, phosphatidylglycerol, and cholesterol was evaluated in vivo following subcutaneous transplantation in mice. Survival of ADSCs co-delivered with liposomal NS3694 was significantly higher than that of untreated ADSCs or ADSCs treated with free NS3694 or empty liposomes. An immunohistochemical analysis revealed a higher number of human nucleus-positive cells after treatment with liposomal NS3694 than following treatment with free NS3694. Similarly, liposomal NS3694 significantly enhanced survival of transplanted ADSCs in rabbits compared to other treatments. Taken together, our results indicate the potential of liposomal NS3694 co-delivered with ADSCs using fibrin gel systems as an in vivo-survival enhancer.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.forename: Saewon
authors.initials: S
authors.lastname: Im
authors.forename: Sangbin
authors.initials: S
authors.lastname: Lee
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Hyerim
authors.initials: H
authors.lastname: Jin
authors.forename: Soondong
authors.initials: S
authors.lastname: Lee
authors.forename: Irang
authors.initials: I
authors.lastname: Im
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Seong Who
authors.initials: SW
authors.lastname: Kim
authors.forename: Taik Jong
authors.initials: TJ
authors.lastname: Lee
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Eom
authors.forename: Tac-Ghee
authors.initials: TG
authors.lastname: Yi
authors.forename: Sun Uk
authors.initials: SU
authors.lastname: Song
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D053478:Apoptosomes / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005337:Fibrin / Q000737:chemistry; D005782:Gels; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D053478:Apoptosomes; D005782:Gels; D008081:Liposomes; C000591229:NS3694; D010671:Phenylurea Compounds; D062367:ortho-Aminobenzoates; D005337:Fibrin
keywords: Apoptosome inhibitor; Co-delivery; Human adipose tissue-derived stem cells; Liposomes; Survival; Transplantation