Generation of a Functioning and Self-Renewing Diaphragmatic Muscle Construct

Caterina Trevisan, Mario Enrique Alvrez Fallas, Edoardo Maghin, Chiara Franzin, Piero Pavan, Paola Caccin, Angela Chiavegato, Eugenia Carraro, Daniele Boso, Francesco Boldrin, Federico Caicci, Enrica Bertin, Luca Urbani, Anna Milan, Carlo Biz, Lorenza Lazzari, Paolo De Coppi, Michela Pozzobon, Martina Piccoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)858-869
JournalStem cells translational medicine
Volume8
Issue number8
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Decellularized scaffold
  • Diaphragm
  • Extracellular matrix
  • Human muscle precursor cells
  • Recellularization

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Trevisan, C., Fallas, M. E. A., Maghin, E., Franzin, C., Pavan, P., Caccin, P., Chiavegato, A., Carraro, E., Boso, D., Boldrin, F., Caicci, F., Bertin, E., Urbani, L., Milan, A., Biz, C., Lazzari, L., De Coppi, P., Pozzobon, M., & Piccoli, M. (2019). Generation of a Functioning and Self-Renewing Diaphragmatic Muscle Construct. Stem cells translational medicine, 8(8), 858-869. https://doi.org/10.1002/sctm.18-0206