Casein-enhanced uptake and disease-modifying bioactivity of ingested extracellular vesicles.

Extracellular vesicles (EVs) from cardiac stromal cells, developed as therapeutic candidates, improve dystrophic muscle function when administered parenterally, but oral delivery remains untested. We find that casein, the dominant protein in breast milk, enhances the uptake and bioactivity of ingested heart-derived EVs, altering gene expression in blood cells and enhancing muscle function in mice with muscular dystrophy. Thus, EVs, administered orally, are absorbed and exert disease-modifying bioactivity .

Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice.

Dystrophin deficiency leads to progressive muscle degeneration in Duchenne muscular dystrophy (DMD) patients. No known cure exists, and standard care relies on the use of antiinflammatory steroids, which are associated with side effects that complicate long-term use. Here, we report that a single intravenous dose of clinical-stage cardiac stromal cells, called cardiosphere-derived cells (CDCs), improves the dystrophic phenotype in mdx mice.

Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy.

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival.

Fibroblasts Rendered Antifibrotic, Antiapoptotic, and Angiogenic by Priming With Cardiosphere-Derived Extracellular Membrane Vesicles.

Background: Cardiosphere-derived cells mediate therapeutic regeneration in patients after myocardial infarction and are undergoing further clinical testing for cardiomyopathy. The beneficial effects of cardiosphere-derived cells are mediated by the secretion of exosomes and possibly other extracellular membrane vesicles (EMVs).

Objectives: This study sought to investigate the effect of cardiosphere-derived EMVs (CSp-EMVs) on fibroblasts in vitro and tested whether priming with CSp-EMVs could confer salutary properties on fibroblasts in vivo.