Generation of a Functioning and Self-Renewing Diaphragmatic Muscle Construct.
Decellularized scaffold
Diaphragm
Extracellular matrix
Human muscle precursor cells
Recellularization
Journal
Stem cells translational medicine
ISSN: 2157-6580
Titre abrégé: Stem Cells Transl Med
Pays: England
ID NLM: 101578022
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
24
09
2018
accepted:
04
03
2019
pubmed:
12
4
2019
medline:
4
6
2020
entrez:
12
4
2019
Statut:
ppublish
Résumé
Surgical repair of large muscular defects requires the use of autologous graft transfer or prosthetic material. Naturally derived matrices are biocompatible materials obtained by tissue decellularization and are commonly used in clinical practice. Despite promising applications described in the literature, the use of acellular matrices to repair large defects has been only partially successful, highlighting the need for more efficient constructs. Scaffold recellularization by means of tissue engineering may improve not only the structure of the matrix, but also its ability to functionally interact with the host. The development of such a complex construct is challenging, due to the complexity of the native organ architecture and the difficulties in recreating the cellular niche with both proliferative and differentiating potential during growth or after damage. In this study, we tested a mouse decellularized diaphragmatic extracellular matrix (ECM) previously described by our group, for the generation of a cellular skeletal muscle construct with functional features. The decellularized matrix was stored using different conditions to mimic the off-the-shelf clinical need. Pediatric human muscle precursors were seeded into the decellularized scaffold, demonstrating proliferation and differentiation capability, giving rise to a functioning three-dimensional skeletal muscle structure. Furthermore, we exposed the engineered construct to cardiotoxin injury and demonstrated its ability to activate a regenerative response in vitro promoting cell self-renewal and a positive ECM remodeling. Functional reconstruction of an engineered skeletal muscle with maintenance of a stem cell pool makes this a promising tool toward future clinical applications in diaphragmatic regeneration. Stem Cells Translational Medicine 2019;8:858&869.
Identifiants
pubmed: 30972959
doi: 10.1002/sctm.18-0206
pmc: PMC6646700
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
858-869Informations de copyright
© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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