Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

Paul E. Bourgine, Celeste Scotti, Sebastien Pigeot, Laurent A. Tchang, Atanas Todorov, Ivan Martin

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.

Original languageEnglish
Pages (from-to)17426-17431
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number49
DOIs
Publication statusPublished - Dec 9 2014

Fingerprint

Extracellular Matrix
Apoptosis
Cartilage
Chondrogenesis
Bone and Bones
Equipment and Supplies
Bone Development
Glycosaminoglycans
Mesenchymal Stromal Cells
Minerals
Regeneration
Cytokines
Proteins

Keywords

  • Developmental engineering
  • Endochondral
  • Extracellular matrix
  • Hematopoisesis
  • Osteoinductive

ASJC Scopus subject areas

  • General

Cite this

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis. / Bourgine, Paul E.; Scotti, Celeste; Pigeot, Sebastien; Tchang, Laurent A.; Todorov, Atanas; Martin, Ivan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 49, 09.12.2014, p. 17426-17431.

Research output: Contribution to journalArticle

Bourgine, Paul E. ; Scotti, Celeste ; Pigeot, Sebastien ; Tchang, Laurent A. ; Todorov, Atanas ; Martin, Ivan. / Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 49. pp. 17426-17431.
@article{283ad83b01a6461788416ab9536d25be,
title = "Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis",
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 ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.",
keywords = "Developmental engineering, Endochondral, Extracellular matrix, Hematopoisesis, Osteoinductive",
author = "Bourgine, {Paul E.} and Celeste Scotti and Sebastien Pigeot and Tchang, {Laurent A.} and Atanas Todorov and Ivan Martin",
year = "2014",
month = "12",
day = "9",
doi = "10.1073/pnas.1411975111",
language = "English",
volume = "111",
pages = "17426--17431",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "49",

}

TY - JOUR

T1 - Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

AU - Bourgine, Paul E.

AU - Scotti, Celeste

AU - Pigeot, Sebastien

AU - Tchang, Laurent A.

AU - Todorov, Atanas

AU - Martin, Ivan

PY - 2014/12/9

Y1 - 2014/12/9

N2 - 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 ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.

AB - 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 ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.

KW - Developmental engineering

KW - Endochondral

KW - Extracellular matrix

KW - Hematopoisesis

KW - Osteoinductive

UR - http://www.scopus.com/inward/record.url?scp=84917694815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84917694815&partnerID=8YFLogxK

U2 - 10.1073/pnas.1411975111

DO - 10.1073/pnas.1411975111

M3 - Article

C2 - 25422415

AN - SCOPUS:84917694815

VL - 111

SP - 17426

EP - 17431

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 49

ER -