Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis.
Bourgine, Paul E. LU
; Scotti, Celeste
; Pigeot, Sebastien
; Tchang, Laurent A.
; Todorova, Atanas
and Martin, Ivan
(2014)
In Proceedings of the National Academy of Sciences
111(49).
p.17426-17431
- Abstract
- 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... (More)
- 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 hypertrophic cartilage ECM, tested in a stringent ectopic 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/d5ab1ef5-7a0b-470c-ae01-f6af8a1f60f1
- author
- Bourgine, Paul E.
LU
; Scotti, Celeste
; Pigeot, Sebastien
; Tchang, Laurent A.
; Todorova, Atanas
and Martin, Ivan
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- in
- Proceedings of the National Academy of Sciences
- volume
- 111
- issue
- 49
- pages
- 17426 - 17431
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:84917694815
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1411975111
- language
- English
- LU publication?
- no
- id
- d5ab1ef5-7a0b-470c-ae01-f6af8a1f60f1
- date added to LUP
- 2022-02-09 19:04:17
- date last changed
- 2022-03-12 07:48:35
@article{d5ab1ef5-7a0b-470c-ae01-f6af8a1f60f1,
abstract = {{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 hypertrophic cartilage ECM, tested in a stringent ectopic 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.}},
author = {{Bourgine, Paul E. and Scotti, Celeste and Pigeot, Sebastien and Tchang, Laurent A. and Todorova, Atanas and Martin, Ivan}},
issn = {{1091-6490}},
language = {{eng}},
number = {{49}},
pages = {{17426--17431}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis.}},
url = {{http://dx.doi.org/10.1073/pnas.1411975111}},
doi = {{10.1073/pnas.1411975111}},
volume = {{111}},
year = {{2014}},
}