Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase.
Biomaterials
; 126: 1-9, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-28237907
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transglutaminases
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Sistemas de Liberação de Medicamentos
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Proteínas de Ligação ao GTP
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Alicerces Teciduais
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Injeções
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China