Table 1.

Animal studies of G-CSF therapy for cardiac repair

Study	Host	Type of ischemia	Duration of therapy	Dose	Follow-up period	Outcomes
Models of acute myocardial infarction
Mouse
Fukuhara et al. [44]	C57BL/6 mouse	Permanent coronary occlusion	3 days before and 5 days after MI	200 μg/kg per day, i.p.	4 weeks	↓ Mortality ↓ Infarct size
Harada et al. [51]	Mouse	Permanent coronary occlusion	Immediately after MI for 5 days	10–100 μg/kg per day, s.c.	1 week	↓ Apoptosis ↓ Infarct size ↑ LVFS Improved hemodynamic parameters
Deindl et al. [29]	C57BL/6 mouse	Permanent coronary occlusion	Immediately after MI for 5 days	100 μg/kg per day, s.c.	30 days	↓ Mortality ↑ LVEF Improved hemodynamic parameters ↔ Infarct size Neovascularization +
Fujita et al. [43]	C57BL/6 mouse	Permanent coronary occlusion	24 h after MI for 10 days	300 μg/kg per day, s.c.	60 days	↑ LVEF Improved hemodynamic parameters ↓ Mortality ↓ Infarct size in chronic phase Myocardial regeneration +
Rat
Sugano et al. [144]	Wistar rat	Permanent coronary occlusion	3 h after MI and every 24 h thereafter for 7 days	20 μg/kg per day, s.c.	2 weeks	↓ LVEDD Improved hemodynamic parameters ↔ Infarct size
Li et al. [92]	Sprague–Dawley rat	Permanent coronary occlusion	Immediately after MI for 5 days	100 μg/kg per day, s.c.	4 weeks	↓ Infarct size ↑ LVEF Improved remodeling Reendothelialization +
Werneck-de-Castro et al. [167]	Wistar rat	Permanent coronary occlusion	3 h after MI for 7 days	100 μg/kg per day, s.c.	19–21 days	↔ Infarct size ↔ LVEF ↔ Hemodynamics ↔ LV remodeling
Cheng et al. [23]	Sprague– Dawley rat	Permanent coronary occlusion	3 h after MI for 5 days	50 μg/kg per day, s.c.	3 months	↓ LVEF ↑ LV dilation Worse hemodynamic parameters ↑ Infarct size ↑ Cardiac fibrosis ↑ Mortality
Ueda et al. [158]	Wistar rat	Ischemia/reperfusion in isolated-perfused hearts	Started at the onset of reperfusion and continued for 2 h	300 ng/mL	2 h	↓ Infarct size ↑ LV diastolic pressure
Ieishi et al. [68]	Wistar rat	2 Groups: permanent coronary occlusion; and ischemia/reperfusion	For 5 days in both the groups	100 μg/kg per day, s.c.	4 weeks	Permanent occlusion: ↔ Infarct size ↔ LV wall thickness ↔ LVEF Ischemia/reperfusion: ↓ Infarct size ↑ LV wall thickness ↑ LVEF
Rabbit
Minatoguchi et al. [108]	Rabbit	Open chest ischemia/reperfusion injury	From 1 to 5 days after MI	10 μg/kg per day, s.c.	3 months	↓ LV dilation ↓ Infarct size ↑ LVEF ↑ Infarct wall thickness
Misao et al. [109]	Rabbit	Ischemia/reperfusion injury	From 3 days to 7 days post-MI	10 μg/kg per day, s.c.	4 weeks	↓ Scar area/LV area ratio ↑ LVEF ↓ LV dimensions
Dog
Takahama et al. [146]	Dog	Open chest ischemia/reperfusion injury	For 30 min from the onset of reperfusion	0.33 μg/kg/min, i.v.	6 h	↓ Arrhythmias ↓ Infarct size
Pig
Iwanaga et al. [73]	Swine	Permanent coronary occlusion	From 24 h after MI to 7 days	10 μg/kg per day, s.c.	4 weeks	↓ Apoptosis ↓ Infarct size ↑ LVEF Neovascularization +
Beohar et al. [10]	Swine	Ischemia/reperfusion injury	Early group: immediately after injury on every other day for 20 days Delayed group: beginning 5 days after injury for 10 days	10 μg/kg per day, i.m.	56 days	Early treatment: ↔ LVEF ↓ LVEDV ↓ Capillary density Delayed treatment: ↑ LVEDV ↓ Capillary density
Angeli et al. [7]	Swine	Ischemia/reperfusion injury	i.v. bolus at reperfusion, daily s.c. injections 5–9 days post-MI	i.v. bolus: 10 μg/kg per day; s.c. injections: 5 μg/kg per day	6 weeks	↑ LVEF ↑ Wall motion score index ↑ Vascular density ↑ Areas of viable myocardium
Models of cardiomyopathy
Mouse
Li et al. [93]	C57BL/6 mouse	Permanent coronary occlusion	12 weeks after MI, on the first 5 days of each week, continued for 4 weeks	10 μg/kg per day, s.c.	16 weeks	↓ Infarct size ↓ Fibrosis ↑ LVEF Improved hemodynamic parameters ↑ Cardiomyocyte size
Tomita et al. [153]	C57BL/6 mouse	Doxorubicin-induced cardiomyopathy	Early group: immediately after doxorubicin injection for 8 days Delayed group: 3 weeks after doxorubicin injection for 8 days	50 μg/kg per day, s.c.	8 weeks	↓ Mortality ↓ Cardiac toxicity Myocardial regeneration +
Li et al. [91]	C57BL/6 mouse	Doxorubicin-induced cardiomyopathy	Immediately after doxorubicin injection for 5 days	100 μg/kg per day, s.c.	10 weeks	↓ LV dilation ↓ Fibrosis ↓ Inflammation ↑ LVEF Improved hemodynamic parameters
Rat
Louzada et al. [96]	Wistar rat	Permanent coronary occlusion	4 weeks after MI, rats were assigned to two protocols. Protocol I: G-CSF daily for 7 days Protocol II: G-CSF for 4 weeks on first 5 days of each week	Protocol I: 50 μg/kg per day, s.c. Protocol II: 10 μg/kg per day, s.c.	10 weeks	↔ LV fractional shortening ↔ Hemodynamics ↔ Infarct size ↔ Hypertrophy
Hou et al. [65]	Wistar rat	Doxorubicin-induced cardiomyopathy	2 weeks after doxorubicin injection for 8 days	50 μg/kg per day, s.c.	4 weeks	↓ Apoptosis ↑ LVEF
Hamster
Miyata et al. [111]	UM-X7.1 hamster	Autosomal recessive cardiomyopathy	5 days/wk from 15 to 30 weeks of age	10 μg/kg per day, s.c.	15 weeks	↓ Mortality Improved remodeling ↓ Fibrosis ↑ LVEF ↑ Cardiomyocyte size
Pig
Hasegawa et al. [54]	Swine	Ameroid-induced chronic coronary occlusion	Immediately after MI for 7 days	10 μg/kg per day, s.c.	4 weeks and 8 weeks	↓ LV dilation ↓ Cardiac fibrosis ↓ Apoptosis ↑ LVEF Improved hemodynamic parameters Neovascularization +

BMC bone marrow cell, G-CSF granulocyte colony-stimulating factor, I.M. intramuscular, I.P. intraperitoneal, I.V. intravenous, LV left ventricular, LVEDD LV end-diastolic diameter, LVEDV LV end-diastolic volume, LVEF LV ejection fraction, LVFS LV fractional shortening, MI myocardial infarction, S.C. subcutaneous, ↑ increased, ↓ decreased, ↔ no change