title: Pharmacokinetics and in vivo fate of intra-articularly transplanted human bone marrow-derived clonal mesenchymal stem cells.
abstract: In this study, we report the pharmacokinetics and in vivo fate of intra-articularly transplanted human mesenchymal stem cells (MSCs) in comparison with those of intravenously administered cells. Bone marrow-derived human clonal mesenchymal stem cells (hcMSCs) were transplanted to nude mice through intravenous or intra-articular routes. The numbers of hcMSCs in blood and tissue samples were measured by the quantitative real-time-polymerase chain reaction (qPCR) with human Alu (hAlu) as a detection marker. Following intra-articular transplantation, the blood levels of hcMSCs peaked 8 h postdose and gradually diminished, showing a 95-fold higher mean residence time than hcMSCs delivered through the intravenous route. Unlike intravenously administered hcMSCs, intra-articularly injected hcMSCs were mainly retained at injection joint sites where their levels 8 h postdose were 116-fold higher than those in muscle tissues. Regardless of injection routes, biodistribution patterns did not significantly differ between normal and osteoarthritis-induced mice. Quantitative analysis using hAlu-specific qPCR revealed that hcMSC levels in joint tissues were significantly higher than those in muscle tissues 120 days postdose. These dramatic differences in kinetic behavior and fate of intra-articularly transplanted hcMSCs compared with intravenously administered hcMSCs may provide insights useful for the development of human MSCs for arthritis therapeutics.
authors.affiliation: 1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.forename: Sangbin
authors.initials: S
authors.lastname: Lee
authors.forename: Jeonghoon
authors.initials: J
authors.lastname: Han
authors.forename: Gunwoo
authors.initials: G
authors.lastname: Kim
authors.forename: Hyerim
authors.initials: H
authors.lastname: Jin
authors.forename: Wenjun
authors.initials: W
authors.lastname: Miao
authors.forename: Tac-Ghee
authors.initials: TG
authors.lastname: Yi
authors.forename: Yun Kyoung
authors.initials: YK
authors.lastname: Cho
authors.forename: Sun Uk
authors.initials: SU
authors.lastname: Song
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D006801:Humans; D007596:Joints / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000166:cytology; D010003:Osteoarthritis / Q000628:therapy