Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia

Valentina Di Felice, Rosario Barone, Eleonora Trovato, Daniela D’amico, Filippo Macaluso, Claudia Campanella, Antonella Marino Gammazza, Vera Muccilli, Vincenzo Cunsolo, Patrizia Cancemi, Gabriele Multhoff, Dario Coletti, Sergio Adamo, Felicia Farina, Francesco Cappello

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an Hsp60-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is directly involved in mitochondrial biogenesis and muscle atrophy suppression, in naïve C2C12 cell lines. Proteomic analyses show Hsp60 localisation inside isolated nanovesicles and the localisation of several apocrine and merocrine molecules, with potential benefits for severe forms of muscle atrophy. Considering that Physiactisome can be easily obtained following tissue biopsy and can be applied to autologous muscle stem cells, we propose a potential nanovesicle-based anti-cachexia drug that could mimic the beneficial effects of exercise. Thus, Physiactisome may improve patient survival and quality of life. Furthermore, the method used to add Hsp60 into nanovesicles can be used to deliver other drugs or active proteins to vesicles.

Original languageEnglish
Article number1406
JournalCells
Volume11
Issue number9
DOIs
StatePublished - 1 May 2022
Externally publishedYes

Keywords

  • cachexia
  • exercise
  • exosome
  • muscle atrophy
  • muscle wasting
  • sarcopenia

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