Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice

Sara Chiappalupi, Giovanni Luca, Francesca Mancuso, Luca Madaro, Francesca Fallarino, Carmine Nicoletti, Mario Calvitti, Iva Arato, Giulia Falabella, Laura Salvadori, Antonio Di Meo, Antonello Bufalari, Stefano Giovagnoli, Riccardo Calafiore, Rosario Donato, Guglielmo Sorci

Research output: Contribution to journalArticle

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration leading to impaired locomotion, respiratory failure and premature death. In DMD patients, inflammatory events secondary to dystrophin mutation play a major role in the progression of the pathology. Sertoli cells (SeC) have been largely used to protect xenogeneic engraftments or induce trophic effects thanks to their ability to secrete trophic, antiinflammatory, and immunomodulatory factors. Here we have purified SeC from specific pathogen-free (SPF)-certified neonatal pigs, and embedded them into clinical grade alginate microcapsules. We show that a single intraperitoneal injection of microencapsulated SPF SeC (SeC-MC) in an experimental model of DMD can rescue muscle morphology and performance in the absence of pharmacologic immunosuppressive treatments. Once i.p. injected, SeC-MC act as a drug delivery system that modulates the inflammatory response in muscle tissue, and upregulates the expression of the dystrophin paralogue, utrophin in muscles through systemic release of heregulin-β1, thus promoting sarcolemma stability. Analyses performed five months after single injection show high biocompatibility and long-term efficacy of SeC-MC. Our results might open new avenues for the treatment of patients with DMD and related diseases.

Original languageEnglish
Pages (from-to)313-326
Number of pages14
JournalBiomaterials
Volume75
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Duchenne muscular dystrophy
  • Engraftment
  • Heregulin
  • Microencapsulation
  • Sertoli cells
  • SPF

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Fingerprint Dive into the research topics of 'Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice'. Together they form a unique fingerprint.

  • Cite this

    Chiappalupi, S., Luca, G., Mancuso, F., Madaro, L., Fallarino, F., Nicoletti, C., Calvitti, M., Arato, I., Falabella, G., Salvadori, L., Di Meo, A., Bufalari, A., Giovagnoli, S., Calafiore, R., Donato, R., & Sorci, G. (2016). Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice. Biomaterials, 75, 313-326. https://doi.org/10.1016/j.biomaterials.2015.10.029