Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

Table 1

Effects of MSC therapy on both small and large animal models of MI. MI, myocardial infarction; DI, direct intramyocardial injection; IV, intravenous infusion; IS, in situ injection; TESI, transendocardial stem cell injection; IC, intracoronary infusion; LV, left ventricular; EF, ejection fraction; ESV, end-systolic volume; EDV, end-diastolic volume; ↑, increase; ↓, decrease. *The monolayered cell graft was placed on a plastic sheet and applied face down onto the surface of the infarct area. The plastic sheet was then carefully removed, leaving the monolayered cell graft on the surface of the heart.

Species/model	Dose	Results	Reference
Mice
Acute MI	0.5-5×10^5(DI)	↓ Both infarct size and fibrosis at 2 weeks	Kudo et al. [68]
Acute MI	3×10^5(DI)	↑ Cardiac function at 4 weeks	Fazel et al. [65]
Acute MI	5×10^5(DI)	↓ Infarct size; ↑ cardiac function at 3 days	Noiseux et al. [70]
Acute MI	1×10^6(DI)	↑ LVEF at 2 and 4 weeks	Nakamura et al. [69]
Acute MI	1×10^6(DI)	↑ Cardiac function at 1 month	Shiota et al. [71]
Acute MI	2×10^5(DI)	↑ LVEF and LV function at 2 weeks	Grauss et al. [67]
Rats
Acute MI	5×10^6(DI)	↓ Cardiac remodeling; ↑ cardiac performance at 2 weeks	Mangi et al. [77]
Acute MI	5×10^6(IV)	↑ Cardiac function; ↓ infarct size at 4 weeks	Nagaya et al. [79]
Acute MI	2×10^6(DI)	Transient global LV function improvement at 4 weeks	Dai et al. [73]
Acute MI	2×10^6(DI)	↓ Fibrosis; ↑ cardiac function at 8 weeks	Berry et al. [72]
Acute MI	Cellgraft^∗	Reversed wall thinning; ↑ cardiac function at 8 weeks	Miyahara et al. [78]
Acute MI	6×10^6(DI)	↑ LVEF; ↓ infarct size at 3 weeks	Li et al. [76]
Acute MI	1×10^6(IS)	↑ LVEF; ↓ infarct size at 30 days	de Macedo Braga et al. [74]
Acute MI	5×10^6(DI)	↑ LVFS; ↓ fibrosis at 4 weeks	Imanishi et al. [75]
Swine
Subacute MI	6×10^7(DI)	↓ Wall thinning in the scar area; ↑ cardiac function at 4 weeks	Shake et al. [92]
Acute MI	2×10^8(TESI)	↓ Necrotic myocardium; ↑ cardiac performance over 8 weeks	Amado et al. [80]
Chronic MI	2×10^8(DI)	Preserved LVEF at 60 and 90 days post-MI	Makkar et al. [86]
Acute MI	2×10^8(TESI)	↓ Infarct size at 1 and 8 weeks; restored contractile function	Amado et al. [81]
Acute MI	3.2×10^8(IV)	↑ LVEF; ↓ hypertrophy at 3 months	Price et al. [87]
Subacute MI	6.3×10^5(TESI)	↓ Scar size; ↓ EDV; ↑ LVEF at 10 days	Gyongyosi et al. [82]
Chronic MI	1-10×10^6(IV)	↑ Vasculogenesis; ↑ regional perfusion; no change in LVEF at 12 weeks	Halkos et al. [83]
Acute MI	0.24-4.4×10^8(TESI)	↓ Scar size; no change in LVEF at 12 weeks	Hashemi et al. [84].
Acute MI	1×10^7(IC)	↑ EF; ↓ scar size at 8 weeks	Qi et al. [88]
Acute MI	2×10^8(TESI)	↑ Myocardial blood flow at 1 week; ↑ LV function at 8 weeks	Schuleri et al. [90]
Chronic MI	2×10^8(TESI)	↓ Scar size; ↑ EF; ↑ regional contractility; ↑ myocardial perfusion over 12 weeks	Quevedo et al. [89]
Chronic MI	0.2-2×10^8(DI)	↓ Scar size; ↑ EF; ↑ regional contractility; ↑ myocardial perfusion at 12 and 24 weeks	Schuleri et al. [91]
Acute MI	0.75-1×10^8(TESI)	↓ Scar size; ↑ EF at 2 and 8 weeks	Hatzistergos et al. [85]
Canine
Chronic ischemia	1×10^8(DI)	↓ Fibrosis; ↑ LVEF at 60 days	Silva et al. [94]
Subacute MI	1×10^8(IC/TESI)	↑ EF; ↓ myocardial ischemia; ↓ EDV and ESV at 21 days post-MI	Perin et al. [93]
Sheep
Acute MI	25-450×10^6(DI)	↓ Infarct expansion; ↑ vascular density in the border zone; ↑ EF; ↓ EDV at 8 weeks	Hamamoto et al. [95]