title: Clearance kinetics of biomaterials affects stem cell retention and therapeutic efficacy.
abstract: The use of biomaterial carriers to improve the therapeutic efficacy of stem cells is known to augment cell delivery, retention, and viability. However, the way that carrier clearance kinetics boosts stem cell delivery and impacts stem cell function remains poorly characterized. In this study, we designed a platform to simultaneously quantify carrier clearance and stem cell retention to evaluate the impact of carrier clearance kinetics on stem cell retention. Additionally, a murine model of hindlimb ischemia was employed to investigate the effects of various cell retention profiles on mitigating peripheral arterial disease. To image the in vivo behaviors of material and cells, we used biotinylated hyaluronan with fluorescently labeled streptavidin and Discosoma sp. Red (Ds-Red)-expressing human mesenchymal stem cells. We found that the retention of transplanted stem cells was closely related to the remaining biomaterial. Furthermore, therapeutic effectiveness was also affected by stem cell retention. These results demonstrate that low-molecular-weight hyaluronan had a slow clearance and high cell retention profile, improving the therapeutic efficacy of human stem cells.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , No. 128 Sec. 2, Academia Road, Taipei 115, Taiwan.
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lai
authors.forename: Pei J
authors.initials: PJ
authors.lastname: Wu
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
authors.forename: Sho T
authors.initials: ST
authors.lastname: Lee
authors.forename: Shiaw M
authors.initials: SM
authors.lastname: Hwang
authors.forename: Shoei S
authors.initials: SS
authors.lastname: Wang
authors.forename: Kuan
authors.initials: K
authors.lastname: Wang
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002478:Cells, Cultured; D006614:Hindlimb / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007511:Ischemia / Q000628:therapy*; D007700:Kinetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D008819:Mice, Nude
chemical_list: D001672:Biocompatible Materials; D006820:Hyaluronic Acid