title: A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.
abstract: Although mesenchymal stem cells (MSCs) present a promising tool in cell therapy for the treatment of various diseases, the in vivo distribution of administered MSCs has still been poorly understood, which hampers the precise prediction and evaluation of their therapeutic efficacy. Here, we developed the first model to characterize the physiological kinetics of administered MSCs based on direct visualization of cell spatiotemporal disposition by intravital microscopy and assessment of cell quantity using flow cytometry. This physiologically based kinetic model was validated with multiple external datasets, indicating potential inter-route and inter-species predictive capability. Our results suggest that the targeting efficiency of MSCs is determined by the lung retention and interaction between MSCs and target organs, including cell arrest, depletion and release. By adapting specific parameters, this model can be easily applied to abnormal conditions or other types of circulating cells for designing treatment protocols and guiding future experiments.
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.|Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 S. Dongfang Road, Shanghai, 200127, China.
authors.forename: Haolu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: School of Medicine, The University of Queensland, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia.
authors.forename: Darrell H G
authors.initials: DH
authors.lastname: Crawford
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.|School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000465:Algorithms; D000818:Animals; D058948:Cell Tracking; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008962:Models, Theoretical