Table 1 Strategies for developing biological pacemakers
From: Harnessing cell reprogramming for cardiac biological pacing
Strategy | Animal/delivery | Beating rate (bpm) | MDP (mV) | APD90 (ms) | If (pA/pF) | Decreased genes | Increased genes | No changes | Duration (days) | References |
|---|---|---|---|---|---|---|---|---|---|---|
Functional re-engineering | ||||||||||
 Adeno-Kir2.1AAA | Guinea pig/LV | 300 | − 60.7 ± 2.1 | – | – | – | – | – | 3–4 | Miake et al. [36] |
 Adeno-HCN2 | Canine/LA appendage | – | – | – | 45.3 ± 12.5 (at − -125 mV) | – | – | – | 3–4 | Qu et al. [29] |
 Adeno-HCN2 | Canine/LBBB | 60 | − 65 | – | 50 (at − 115 mV) | – | – | – | 7 | Plotnikov et al. [37] |
 Adeno-HCN2 (E324A) | Canine/LBBB | 52 | – | – | 21.0 ± 3.5 (at − 125 mV) | – | – | – | 14 | Bucchi et al. [42] |
 Adeno-HCN2/SkM1 | Canine/LB | 80 | − 85 ± 1 | 224 ± 9 | – | – | – | – | 7 | Boink et al. [33] |
 Adeno-SK4/HCN2 | Rat/LV | 139.9 ± 21.9 | – | 82.5 ± 12.8 | – | – | Kcnn4 Hcn2 | – | 5–7 | Zhao et al. [121] |
Cell-gene hybrid approach | ||||||||||
 Lenti-HCN1-fibroblasts fused with myocytes | Guinea pig/LV | 180 | − 54 | – | − 54 (at − 125 mV) | – | – | – | 22 | Cho et al. [40] |
 pIRSE-HCN2-MSCs | Canine/LVE | 60 | – | – | – | – | – | – | 42 | Plotnikov et al. [43] |
 Lenti-HCN4-MSCs | Canine/LVE | 59 ± 5 | – | – | 26.1 ± 3.6 (at − 140 mV) | – | Hcn4 | – | 42 | Lu et al. [46] |
 Lenti-HCN2/SkM1-CPCs | Mice/LV | – | – | – | – | – | – | – | 7 | Végh et al. [47] |
Direct reprogramming | ||||||||||
 Tbx3 transgenic mice | Mice | 32 | − 60 | 164 | – | Cx43 Cx40 Scn5a Nppa Kir2.1 Kir3.1 Kir2.2 | Hcn1 Lbh | Hcn2 Hcn4 | 5 | Bakker et al. [53] |
 Adeno-Tbx18 | Guinea pig/LV | 135 | − 37 | 119 |  | Cx43 Kir2.1 Nav1.5 PLB Nkx2-5 α-actinin | P-PLB | Serca2a Ncx1 Ryr | 28 | Kapoor et al. [51] |
 Adeno-Tbx18 | Pig/RV septum | 58 | – | 274 | – | Nav1.5 Nkx2.5 Kir2.1 Cx43 | Hcn4 | Cx45 α-actinin | 14 | Hu et al. [91] |
 CMmTbx18 with antagomirs | Rat/LV | 97 | – | – | – | Cx43 SCN5a Nkx2.5 | Hcn2 Hcn4 Tbx18 |  | 5 | Sanchez et al. [58] |
 Biomaterials (silk fibroin) | Rat/LV | 137 | − 59 | – | 18 (at −  150 mV) | Myl2 Cx43 | P-PLB Hcn4 Cx45 Cx40 | Nkx2.5 | 56 | Hu et al. [64] |
Human induced pluripotent stem cell-derived pacemaker cardiomyocytes | ||||||||||
 Lenti-Tbx18-hiPSC-CMs | Rat/LV | 219 ± 18 | – | – | – | Cx43 | Tbx18 Hcn4 | – | 14 | Gorabi et al. [122] |
 HiPSC-CMs | Canine/LV | 69 ± 10.4 | – | – | − 87 (at − 120 mV) | Nanog Okt-4 Pou5flc12 Pou5flc1 Pou5flc8 Utf1 Nodal Tdgf1 | Nkx2.5 Anf Csrp3 Phospholamban Des Myh6 Myh7 Tnnt4 | – | 91 | Chauveau et al. [44] |