Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28237907.
- Also identified by DOI 10.1016/j.biomaterials.2017.02.021.
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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 CCl<sub>4</sub>-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.
Medical subject headings
- Drug Delivery Systems
- GTP-Binding Proteins
- Injections
- Tissue Scaffolds
- Transglutaminases