title: Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase.
abstract: Targeted cell delivery to lesion sites via minimally invasive approach remains an unmet need in regenerative medicine to endow satisfactory therapeutic efficacy and minimized side-effects. Here, we rationally designed a pathology-targeted cell delivery strategy leveraging injectable micro-scaffolds as cell-loading capsule and endogenous tissue transglutaminase (TGase) at lesion site as adhesive. Up-regulated TGase post-liver injury catalyzed chemical bonding between the glutamine and lysine residues on liver surface and micro-scaffolds both ex vivo and in vivo, facilitating sufficient adhesion on the pathological liver. Upon intraperitoneal injection, Mesenchymal Stem Cell-loaded capsules, exhibiting cell protection from shear-induced damage and post-transplantation anoikis, adhered to the CCl4-treated liver with a hundred-fold improvement in targeting efficiency (70.72%) compared to free-cell injection, which dramatically improved mice survival (33.3% vs. 0% for free-cell therapy) even with low-dosage treatment. This unique and widely-applicable cell delivery mechanism and strategy hold great promise for transforming cell therapy for refractory diseases.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Badger
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. Electronic address: duyanan@tsinghua.edu.cn.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002214:Capsules; D002448:Cell Adhesion; D016503:Drug Delivery Systems; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007267:Injections; D008099:Liver / Q000293:injuries / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D054457:Tissue Scaffolds / Q000737:chemistry*; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D002214:Capsules; D011092:Polyethylene Glycols; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Cell therapy; Endogenous TGase; Micro-scaffold capsule; Pathological liver; Targeted cell delivery