Adipose‑derived stem cells overexpressing SK4 calcium‑activated potassium channel generate biological pacemakers.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Recent studies have suggested that calcium‑activated potassium channel (KCa) agonists increase the proportion of mouse embryonic stem cell‑derived cardiomyocytes and promote the differentiation of pacemaker cells. In the present study, it was hypothesized that adipose‑derived stem cells (ADSCs) can differentiate into pacemaker‑like cells via overexpression of the SK4 gene. ADSCs were transduced with a recombinant adenovirus vector carrying the mouse SK4 gene, whereas the control group was transduced with GFP vector. ADSCs transduced with SK4 vector were implanted into the rat left ventricular free wall. Complete atrioventricular block (AVB) was established in isolated perfused rat hearts after 2 weeks. SK4 was successfully and stably expressed in ADSCs following transduction. The mRNA levels of the pluripotent markers Oct‑4 and Sox‑2 declined and that of the transcription factor Shox2 was upregulated following SK4 transduction. The expression of α‑actinin and hyperpolarization‑activated cyclic nucleotide‑gated potassium channel 4 (HCN4) increased in the SK4 group. The hyperpolarizing activated pacemaker current If (8/20 cells) was detected in ADSCs transduced with SK4, but not in the GFP group. Furthermore, SK4 transduction induced the expression of p‑ERK1/2 and p‑p38 MAPK. In the ex vivo experiments, the heart rate of the SK4 group following AVB establishment was significantly

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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