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Media type:
E-Article
Title:
Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis
Contributor:
Bourgine, Paul E.;
Scotti, Celeste;
Pigeot, Sebastien;
Tchang, Laurent A.;
Todorov, Atanas;
Martin, Ivan
Published:
National Academy of Sciences, 2014
Published in:
Proceedings of the National Academy of Sciences of the United States of America, 111 (2014) 49, Seite 17426-17431
Language:
English
ISSN:
0027-8424
Origination:
Footnote:
Description:
<p>The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developmental processes. The paradigm was exemplified in the context of the skeletal system by testing the osteoinductive capacity of engineered and devitalized hypertrophic cartilage, which is the primordial template for the development of most bones. ECM was engineered by inducing chondrogenesis of human mesenchymal stromal cells and devitalized by the implementation of a death-inducible genetic device, leading to cell apoptosis on activation and matrix protein preservation. The resulting hypertrophie cartilage ECM, tested in a stringent ectopie implantation model, efficiently remodeled to form de novo bone tissue of host origin, including mature vasculature and a hematopoietic compartment. Importantly, cartilage ECM could not generate frank bone tissue if devitalized by standard "freeze & thaw" (F&T) cycles, associated with a significant loss of glycosaminoglycans, mineral content, and ECM-bound cytokines critically involved in inflammatory, vascularization, and remodeling processes. These results support the utility of engineered ECM-based devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.</p>