Table 1.
Pre‐clinical effects of cell therapy on cardiac function and rhythm
| Cell timing + delivery | ||||
|---|---|---|---|---|
| Cell type | Animal model | method | Cell transplant results | Reference |
| SkMs | Rats + LAD coronary artery ligation | 7 days post‐surgery + IC injection | 13/20 SkM‐treated rats had sustained ventricular tachycardia at electrophysiological testing. | Fernandes et al. (2006) |
| SkMs | Mice + cryolesion | At surgery + intra‐cardiac injection | 15/16 SkM‐treated mice had sustained ventricular tachycardia at electrophysiological testing. | Roell et al. (2007) |
| Over‐expression of Cx43 decreased SkM induced ventricular tachycardia by 62.5% at electrophysiological testing. | ||||
| MSCs | Pigs + catheter infarction | 1 month post‐infarct + catheter injection | Increased cardiac nerve sprouting no evidence for pro‐arrhythmia but not formally assessed. | Pak et al. (2003) |
| BMCs | Rats + LAD coronary artery ligation | 7 days post‐surgery + intra‐cardiac injection | No increase in sustained ventricular tachycardia at electrophysiological testing. | Fernandes et al. (2006) |
| MSCs | Pigs + catheter infarction | 30 min post infarct + intravenous infusion | Improved cardiac function but decreased refractoriness 3 months post‐cell transplant. | Price et al. (2006) |
| Human ESC‐CMs | Nude rats + LAD coronary artery ligation | 4 day post‐surgery + intra‐cardiac injection | Improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Laflamme et al. (2007) |
| ESC‐CMs | Mice + LAD coronary artery ligation | At surgery+ intra‐cardiac injection | Improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Ebert et al. (2007) |
| ESC‐CMs | Mice + cryolesion | At surgery + intra‐cardiac injection | Decrease sustained ventricular tachycardia at electrophysiological testing. | Roell et al. (2007) |
| Human ESC‐CMs | Immuno‐suppressed guinea‐pigs + cryolesion | 10 days post‐surgery + intra‐cardiac injection | Improved cardiac function while reducing spontaneous and inducible ventricular tachycardia | Shiba et al. (2012) |
| Human ESC‐CMs | Immuno‐suppressed macaques + catheter infarction | 14 days post infarct + catheter injection | 4/4 ESC‐CM treated macaques demonstrated premature ventricular contractions and spontaneous ventricular tachycardia. | Chong et al. (2014) |
| iPSCs | Mice + LAD coronary artery ligation | At surgery + intra‐cardiac injection | Improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Singla et al. (2011) |
| Human iPSC‐CM | Nude rats + LAD coronary artery ligation | At surgery | Trend to improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Carpenter et al. (2012) |
| Human iPSC‐CM | Immuno‐suppressed pigs + LAD constriction | 4 weeks post‐surgery | Improved cardiac function with no evidence for pro‐arrhythmia on 24 telemetry prior to sacrifice 8 weeks after cell delivery. | Kawamura et al. (2012) |
| iPSCs | Pigs + catheter infarction | 7 days post‐infarct | Improved cardiac function and perfusion with no evidence for pro‐arrhythmia but not formally assessed. | Li et al. (2013) |
| EDCs + CDCs | Rats + LAD coronary artery ligation | At surgery + intra‐cardiac injection | Both EDCs and CDCs improved cardiac function to a similar degree with no evidence for pro‐arrhythmia but not formally assessed. | Davis et al. (2010 a) |
| Human EDCs | SCID Mice + LAD coronary artery ligation | 7 days post‐infarct + intra‐cardiac injection | Improved cardiac function with enhanced EDC engraftment and no evidence for pro‐arrhythmia but not formally assessed. | Mayfield et al. (2014 b) |
| Human EDCs | SCID Mice + LAD coronary artery ligation | 7 days post‐infarct + intra‐cardiac injection | Diabetes impairs the EDC‐mediated improvements in cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Molgat et al. (2014) |
| Human EDCs + EPCs | SCID Mice + LAD coronary artery ligation | 7 days post‐infarct + intra‐cardiac injection | Both EDCs and EPCs improved cardiac function to a similar degree with no evidence for pro‐arrhythmia but not formally assessed. | Latham et al. (2013) |
| Human c‐Kit+ cells | SCID Mice and rats + LAD coronary artery ligation | At surgery + intra‐cardiac injection | Improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Bearzi et al. (2007) |
| Cardiospheres | Mice + LAD coronary artery ligation | At surgery + intra‐cardiac injection | Improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Messina et al. (2004) |
| Human CDCs | SCID Mice + LAD ligation | At surgery + intra‐cardiac injection | CDCs improved cardiac function with no evidence for pro‐arrhythmia but not formally assessed. | Smith et al. (2007) |
| Human cardiospheres + CDCs | SCID Mice + LAD ligation | At surgery + intra‐cardiac injection | Cardiospheres improved cardiac function more than CDCs. No evidence for pro‐arrhythmia but not formally assessed. | Li et al. (2010) |
| CDCs | Pig + catheter infarction | 4 weeks post‐infarct + catheter injection | CDCs improved cardiac function while not increasing inducible ventricular tachycardia on electrophysiological testing. | Johnston et al. (2009) |
| CDCs or cardiospheres | Pig + catheter infarction | 4–5 weeks post‐infarct + catheter injection | CDCs and cardiospheres improved cardiac function to a similar extent while not resulting in deaths (sudden or otherwise) in either group. | Lee et al. (2011) |