Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo.

Alveolar macrophages (AMs) are lung tissue-resident macrophages that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that mouse long-term ex vivo expanded AMs (exAMs) maintained a core AM gene expression program, but showed culture adaptations related to adhesion, metabolism and proliferation. Upon transplantation into the lung, exAMs reacquired full transcriptional and epigenetic AM identity, even after several months in culture and could self-maintain long-term in the alveolar niche. Changes in open chromatin regions observed in culture were fully reversible in transplanted exAMs and resulted in a gene expression profile indistinguishable from resident AMs. Our results indicate that long-term proliferation of AMs in culture did not compromise cellular identity in vivo. The robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of exAMs.

Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages.

Loss of muscle mass and strength is a major problem during aging and the expression of Mechano Growth Factor (MGF), a member of the IGF-1 (insulin-like Growth Factor 1) super family, has been shown to be both exercise and age dependent. MGF, also called IGF-1Ec, has a unique E domain with a 49bp insert in humans (52bp in rodents; IGF-1Eb), which results in a reading frame shift during the IGF-1 gene splicing to produce a distinct mature isoform. We have studied the effects of the MGF-24aa-E peptide on proliferation and differentiation of primary human muscle cell cultures isolated from healthy subjects of different ages. We found that MGF-E peptide significantly increases the proliferative life span and delays senescence of satellite cells isolated from neonatal and young adult but not from old adult muscle, hypertrophy associated with a significant decrease in the percentage of reserve cells was observed in all cultures. It is concluded that the MGF-24aa-E peptide alone has a marked ability to enhance satellite cell activation, proliferation and fusion for muscle repair and maintenance and could provide a new strategy to combat age related sarcopenia without the oncogenic side effects observed for IGF1.