PROKR1 delivery by cell-derived vesicles restores the myogenic potential of Prokr1-deficient C2C12 myoblasts.

Cell-derived vesicles (CDVs) have been investigated as an alternative to exosomes. Here, we generated CDVs from Prokineticin receptor 1 (PROKR1) overexpressing HEK293T cells using micro-extrusion. More than 60 billion PROKR1-enriched CDV (PROKR1Tg CDVs) particles with canonical exosome properties were recovered from 107 cells. With 25 µg/mL of PROKR1Tg CDVs, we observed delivery of PROKR1, significant reduction of apoptosis, and myotube formation in C2C12Prokr1-/- myoblasts that have lost their myogenic potential but underwent apoptosis following myogenic commitment. Expression levels of early and late myogenic marker genes and glucose uptake capacity were restored to equivalent levels with wild-type control. Furthermore, PROKR1Tg CDVs were accumulated in soleus muscle comparable to the liver without significant differences. Therefore, CDVs obtained from genetically engineered cells appear to be an effective method of PROKR1 protein delivery and offer promise as an alternative therapy for muscular dystrophy.

Ultrahigh Stability and Operation Performance in Bi-doped GeTe/Sb2Te3 Superlattices Achieved by Tailoring Bonding and Structural Properties.

Changes in bond types and the reversible switching process between metavalent and covalent bonds are related to the operating mechanism of the phase-change (PC) behavior. Thus, controlling the bonding characteristics is the key to improving the PC memory performance. In this study, we have controlled the bonding characteristics of GeTe/Sb2Te3 superlattices (SLs) via bismuth (Bi) doping. The incorporation of Bi into the GeTe sublayers tailors the metavalent bond. We observed significant improvement in device reliability, set speed, and power consumption induced upon increasing Bi incorporation. The introduction of Bi was found to suppress the change in density between the SET and RESET states, resulting in a significant increase in device reliability. The reduction in Peierls distortion, leading to a more octahedral-like atomic arrangement, intensifies electron-phonon coupling with increased bond polarizability, which are responsible for the fast set speed and low power consumption. This study demonstrates how the structural and thermodynamic changes in phase change materials alter phase change characteristics due to systematic changes of bonding and provides an important methodology for the development of PC devices.

Cellhesion VP enhances the immunomodulating potential of human mesenchymal stem cell-derived extracellular vesicles.

Mesenchymal stem cell (MSC) transplantation is a promising therapy for regenerative medicine. However, MSCs grown under two-dimensional (2D) culture conditions differ significantly in cell shape from those in the body, with downregulated stemness genes and secretion of paracrine factors. Here, we evaluated the effect of 3D culture using Cellhesion VP, a water-insoluble material composed of chitin-based polysaccharide fibers, on the characteristics of human Wharton's jelly-derived MSCs (hMSCs). Cellhesion VP significantly increased cell proliferation after retrieval. Transcriptome analyses suggested that genes involved in cell stemness, migration ability, and extracellular vesicle (EV) production were enhanced by 3D culture. Subsequent biochemical analyses showed that the expression levels of stemness genes including OCT4, NANOG, and SSEA4 were upregulated and migration capacity was elevated in 3D-cultured hMSCs. In addition, EV production was significantly elevated in 3D cells, which contained a distinct protein profile from 2D cells. Gene and drug connectivity analyses revealed that the 2D and 3D EVs had similar functions as immunomodulators; however, 3D EVs had completely distinct therapeutic profiles for various infectious and metabolic diseases based on activation of disease-associated signaling pathways. Therefore, EVs from Cellhesion VP-primed hMSCs offer a new treatment for immune and metabolic diseases.