Reaching out: junctions between cardiac telocytes and cardiac stem cells in culture

Telocytes ( TC s) were previously shown by our group to form a tandem with stem/progenitor cells in cardiac stem cell ( CSC ) niches, fulfilling various roles in cardiac renewal. Among these, the ability to ‘nurse’ CSC s in situ , both through direct physical contact (junctions) as well as at a distance, by paracrine signalling or through extracellular vesicles containing mRNA . We employed electron microscopy to identify junctions (such as gap or adherens junctions) in a co‐culture of cardiac TC s and CSC s. Gap junctions were observed between TC s, which formed networks, however, not between TC s and CSC s. Instead, we show that TC s and CSC s interact in culture forming heterocellular adherens junctions , as well as non‐classical junctions such as puncta adherentia and stromal synapses . The stromal synapse formed between TC s and CSC s (both stromal cells) was frequently associated with the presence of electron‐dense nanostructures (on average about 15 nm in length) connecting the two opposing membranes. The average width of the synaptic cleft was 30 nm, whereas the average length of the intercellular contact was 5 μm. Recent studies have shown that stem cells fail to adequately engraft and survive in the hostile environment of the injured myocardium, possibly as a result of the absence of the pro‐regenerative components of the secretome (paracrine factors) and/or of neighbouring support cells. Herein, we emphasize the similarities between the junctions described in co‐culture and the junctions identified between TC s and CSC s in situ . Reproducing a CSC niche in culture may represent a viable alternative to mono‐cellular therapies.