Table 1 Animal models

From: Progress and challenges in transplantation of human pluripotent stem cell derived cardiomyocytes for cardiac therapy

Title	Reference	Animal model	Treatment type	Injury model	Treatment delivery timepoint	Experiment final endpoint	Cell species	Cell types included	Culture duration	Scaffold material	hPSC-CMs dose	Total cell dose
Human ES cell derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts	³⁸	Guinea pig	Single cell suspension	Cryoinjury	10 days post injury	28 days post-transplant	Human	hPSC-CM	2–3 weeks	n/a	1*10⁸	1*10⁸
Human embryonic stem cell derived cardiomyocytes regenerate non human primate hearts	³³	Monkey	Single cell suspension	Ischemia reperfusion (90 min)	14 days post injury	84 days post-transplant	Human	hPSC-CM	16–20 days	n/a	1*10⁹	1*10⁹
Allogenic transplantation of IPS cell derived cardiomyocytes regenerates primate hearts	⁹¹	Monkey	Single cell suspension	Ischemia reperfusion (3 h)	14 days post injury	84 days post-transplant	Monkey	CMs	17 days	n/a	4*10⁸	4*10⁸
Human embryonic stem cell derived cardiomyocytes restores function in infarcted hearts of non human primates	⁴¹	Monkey	Single cell suspension	Ischemia reperfusion (3 h)	14 days post injury	12 weeks post-transplant	Human	hPSC-CM	21 days	n/a	7.5*10⁸	7.5*10⁸
Cardiomyocytes derived from human embryotic stem cells in pro-survival factors enhance function of infarcted rat hearts	⁵⁶	Rat	Single cell suspension	Ischemia reperfusion	4 days post injury	4 weeks post-transplant	Human	hPSC-CM	2–3 weeks	n/a	10*10⁶	10*10⁶
Electrical integration of human embryonic stem cell derived cardiomyocytes in a guinea pig chronic infarct model	⁵⁹	Guinea pig	Single cell suspension	Cryoinjury	28 days post injury	4 weeks post-transplant	Human	hPSC-CM	15–17 days	n/a	80*10⁶	80*10⁶
Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy	⁸¹	Pig	Single cell suspension	Healthy	No injury	7 weeks post-transplant	Human	hPSC-CM	18–20 days	n/a	150*10⁶	150*10⁶
Human embryonic stem cell derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats	⁵⁴	Rat	Single cell suspension	Ischemia reperfusion	1 month post injury	3 months post-transplant	Human	hPSC-CM	2–3 weeks	n/a	10*10⁶	10*10⁶
Non contractile stem cell cardiomyocytes preserve post infarction heart function	⁶⁵	Rat	Single cell suspension	Ischemia reperfusion	4 days post injury	84 days post-transplant	Human	hPSC-CM	20 days	n/a	1*10⁸	1*10⁸
Cellular heterogeneity of pluripotent stem cell derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias	²²	Pig: landrace	Single cell suspension	Ischemia reperfusion	17 days post injury	28 days post-transplant	Human	hPSC-CM	15 days	n/a	750*10⁶	750*10⁶
Regeneration of nonhuman primate hearts with human induced pluripotent stem cell derived cardiac spheroids	¹³	Monkey	Spheroids	Ischemia reperfusion	14 days post injury	84 days post-transplant	Human	hPSC-CM	2–3 weeks hPSC-CMs	n/a	2*10⁷	2*10⁷
	¹³	Monkey	Spheroids	Ischemia reperfusion	14 days post injury	84 days post-transplant	Human	hPSC-CM	9 days spheroids	n/a	6*10⁷	6*10⁷
Intramyocardial transplantation of human ips cell derived cardiac spheroids improves cardiac function in heart failure animals	¹⁰	Pig	Spheroids	Cryoinjury	4 weeks post injury	8 weeks post-transplant	Human	hPSC-CM	2–3 weeks hPSC-CMs	n/a	1*10⁸	1*10⁸
	¹⁰	Pig	Spheroids	Cryoinjury	4 weeks post injury	8 weeks post-transplant	Human	hPSC-CM	9 days spheroids	n/a	1*10⁸	1*10⁸
Spheroids of cardiomyocytes derived from human induced pluripotent stem cells improve recovery from myocardial injury in mice	⁵³	Mouse	Spheroids/Patch	LAD ligation	Day of injury	4 weeks post-transplant	Human	hPSC-CM	16 days hPSC-CMs	Fibrin	10*10⁵	10*10⁵
	⁵³	Mouse	Spheroids/Patch	LAD ligation	Day of injury	4 weeks post-transplant	Human	hPSC-CM	7 days spheroids	Fibrin	10*10⁵	10*10⁵
Implanted human cardiac spheroids electrically couple with infarcted swine myocardium	⁹²	Pig	Spheroids	Ischemia reperfusion	0 days post injury	1 week post-transplant	Human	hPSC-CM	12 days	n/a	50*10⁶	50*10⁶
Nanowired human cardiac organoids transplantation enables highly efficient and effective recovery of infarcted hearts	⁹	Rat	Organoids	Ischemia reperfusion	4 days post injury	28 days post-transplant	Human	hPSC-CM (55%), HUVEC (14%), FB (24%), ADSC (7%)	14 days hPSC-CMs	n/a	500*10³	~909*10³
	⁹	Rat	Organoids	Ischemia reperfusion	4 days post injury	28 days post-transplant	Human	hPSC-CM (55%), HUVEC (14%), FB (24%), ADSC (7%)	4 days organoids	n/a	500*10³	~909*10³
Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts	⁷	Rat	Patch	Permanent LAD ligation	14 days post injury	28 days post-transplant	Rat	CMs	17–19 days	Collagen	2.5* 10⁶ (*5)	2.5* 10⁶ (*5)
Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model	⁵⁵	Rat	Patch	Ischemia reperfusion	1 month post injury	28 days post-transplant	Rat	CMs	17–19 days	Collagen 1	2.510⁶ (2)	2.510⁶ (2)
Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells	¹²	Guinea pig	Patch	Cryoinjury	7 days post injury	28 days post-transplant	Human	hPSC-CM	14 days	Fibrin	1*10⁷	1*10⁷
Human engineered heart tissue patches remuscularize the injured heart in a dose-dependent manner	⁵¹	Guinea pig	Patch	Cryoinjury	7 days post injury	4 weeks post-transplant	Human	hPSC-CM	14 days	Fibrin	4.5-12*10⁶	4.5–12*10⁶
Human ipcs cell derived engineered heart tissue does not affect ventricular arrhythmias in a guinea pig cryoinjury model	⁵⁰	Guinea pig	Patch	Cryoinjury	7 days post injury	28 days post-transplant	Human	hPSC-CM, endothelial cells	14 days	Fibrin	5*10⁶	7*10⁶
Physiological function and transplantation of scaffold free and vascularized human cardiac muscle tissue	⁴⁸	Rat	Patch	Healthy	No injury	7 days post-transplant	Human	hPSC-CM, endothelial cells, fibroblasts	13–15 days hPSC-CMs	n/a	2*10⁶	5*10⁶ (1:1:0.5)
	⁴⁸	Rat	Patch	Healthy	No injury	7 days post-transplant	Human	hPSC-CM, endothelial cells, fibroblasts	8–11 days patch	n/a	2*10⁶	5*10⁶ (1:1:0.5)
Enhanced electrical integration of engineered human myocardium via intramyocardial versus epicardial delivery in infarcted rat hearts	³⁹	Rat	Single cell suspension	Ischemia reperfusion	4 days post injury	4 weeks post-transplant	Human	hPSC-CM	21–24 days	n/a	10*10⁶	10*10⁶
			Spheroids					hPSC-CM	1 days	n/a	10*10⁶	10*10⁶
			Patch					hPSC-CM	6-7 days	n/a	10*10⁶	10*10⁶
Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell derived cardiovascular cell populations	⁵⁷	Pig	Single cell suspension	Ischemia reperfusion	Day of injury	4 weeks post-transplant	Human	hPSC-CM	2–3 weeks	n/a	6*10⁶	6*10⁶
			Single cell suspension					hPSC-CM, endothelial cells, SMC		n/a	2*10⁶	6*10⁶ (1:1:1)
			Patch					hPSC-CM, endothelial cells, SMC		Fibrin	2*10⁶	6*10⁶ (1:1:1)

Table of important animal model experiments.
n/a not applicable.

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Table 1 Animal models

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