Table 2 Studies involving biological pacemakers in large animals
From: Harnessing cell reprogramming for cardiac biological pacing
Studies | Year | Mechanism | Biological agents | Delivery methods | Target animals (injection site) | Functional duration | Monitor device | Backup electronic pacemakers |
|---|---|---|---|---|---|---|---|---|
Functional re-engineering | ||||||||
 Edelberg et al. [39] | 2001 | β2-adrenergic receptors | Plasmid pBR322-β actin promoter-β2 adrenergic receptor | Transvenous | Healthy swine (RA) | 4 days | Repeated ECGs | No |
 Qu et al. [29] | 2003 | HCN2 | AdGFP-HCN2 | Thoracotomy | Healthy canine (LAA) | 4 days | Continuous ECGs on day 4 | No |
 Plotnikov et al. [37] | 2004 | HCN2 | AdGFP-HCN2 | Transarterial | Healthy canine (LB) | 7 days | Continuous 24-h Holter | No |
 Bucchi et al. [42] | 2006 | HCN2 | AdGFP-HCN2 AdGFP-E324A | Transarterial | Canine with CAVB (LB) | 14 days | Continuous 24-h Holter | Yes |
 Tse et al. [96] | 2006 | HCN1 | AdGFP-HCN1Delta | Thoracotomy | Swine with SSS (LAA) | 14 days | Repeated ECGs | Yes |
 Plotnikov et al. [123] | 2008 | HCN2 | AdGFP-HCN212 | Transarterial | Canine with CAVB (LBB) | 14 days | Continuous 24-h Holter | Yes |
 Shlapakova et al. [92] | 2010 | HCN2 | AdGFP-HCN2 | Transarterial | Canine with CAVB (LBB) | 7 days | 24-h Holter at day 1 and day 7 | Yes |
 Cingolani et al. [38] | 2012 | HCN2 and Kir2 | AdGFP-HCN2 + Kir2.1AAA | Transvenous | Swine with CAVB (AVJ) | 14 days | Intermittent 24-h Holter on day 7 and day 14 | Yes |
 Boink et al. [33] | 2013 | HCN2 | AdGFP-HCN2/SkM1 AdGFP-HCN2 AdGFP-SkM1 | Transarterial | Canine with CAVB (LB, LV) | 7 days | Intermittent 24-h Holter from day 5 to day 7 | Yes |
Cell-gene hybrid approach | ||||||||
 Potapova et al. [95] | 2004 | hMSC-HCN2 | HCN2-expressing hMSCs | Thoracotomy | Healthy canine (LV) | 10 days | Repeated ECGs | No |
 Plotnikov et al. [43] | 2007 | hMSC-HCN2 | HCN2-expressing hMSCs | Thoracotomy | Canine with CAVB (LV) | 6 weeks | 24-h Holter weekly | Yes |
Direct reprogramming | ||||||||
 Hu et al. [91] | 2014 | Tbx18 | AdGFP-Tbx18 | Transvenous | Swine with CAVB (RV septum) | 14 days | Real-time, continuous ECG telemetry | Yes |
Human induced pluripotent stem cell-derived pacemaker cardiomyocytes | ||||||||
 Chauveau et al. [44] | 2017 | iPSC | iPSC-derived embryonic body | Thoracotomy | Canine with CAVB (Epicardium of LV) | 3 months | 24-h Holter biweekly | Yes |